NIX-Mediated Mitophagy Promotes Effector Memory Formation in Antigen-Specific CD8+ T Cells
Identifieur interne : 000854 ( Pmc/Curation ); précédent : 000853; suivant : 000855NIX-Mediated Mitophagy Promotes Effector Memory Formation in Antigen-Specific CD8+ T Cells
Auteurs : Shubhranshu S. Gupta [États-Unis] ; Robert Sharp [États-Unis] ; Colby Hofferek [États-Unis] ; Le Kuai [États-Unis] ; Gerald W. Dorn [États-Unis] ; Jin Wang [États-Unis] ; Min Chen [États-Unis]Source :
- Cell reports [ 2211-1247 ] ; 2019.
Abstract
Autophagy plays a critical role in the maintenance of immunological memory. However, the molecular mechanisms involved in autophagy-regulated effector memory formation in CD8+ T cells remain unclear. Here we show that deficiency in NIX-dependent mitophagy leads to metabolic defects in effector memory T cells. Deletion of NIX caused HIF1α accumulation and altered cellular metabolism from long-chain fatty acid to short/branched-chain fatty acid oxidation, thereby compromising ATP synthesis during effector memory formation. Preventing HIF1α accumulation restored long-chain fatty acid metabolism and effector memory formation in antigen-specific CD8+ T cells. Our study suggests that NIX-mediated mitophagy is critical for effector memory formation in T cells.
Url:
DOI: 10.1016/j.celrep.2019.10.032
PubMed: 31722203
PubMed Central: 6886713
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Gupta</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX 77030</wicri:regionArea></affiliation></author><author><name sortKey="Sharp, Robert" sort="Sharp, Robert" uniqKey="Sharp R" first="Robert" last="Sharp">Robert Sharp</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030</wicri:regionArea></affiliation></author><author><name sortKey="Hofferek, Colby" sort="Hofferek, Colby" uniqKey="Hofferek C" first="Colby" last="Hofferek">Colby Hofferek</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030</wicri:regionArea></affiliation></author><author><name sortKey="Kuai, Le" sort="Kuai, Le" uniqKey="Kuai L" first="Le" last="Kuai">Le Kuai</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030</wicri:regionArea></affiliation></author><author><name sortKey="Dorn, Gerald W" sort="Dorn, Gerald W" uniqKey="Dorn G" first="Gerald W." last="Dorn">Gerald W. Dorn</name><affiliation wicri:level="1"><nlm:aff id="A3">Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Jin" sort="Wang, Jin" uniqKey="Wang J" first="Jin" last="Wang">Jin Wang</name><affiliation wicri:level="1"><nlm:aff id="A4">Immunobiology and Transplant Science Center, Houston Methodist Research Institute, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Immunobiology and Transplant Science Center, Houston Methodist Research Institute, Houston, TX 77030</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A5">Department of Surgery, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery, Weill Cornell Medical College, Cornell University, New York, NY 10065</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Min" sort="Chen, Min" uniqKey="Chen M" first="Min" last="Chen">Min Chen</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX 77030</wicri:regionArea></affiliation><affiliation><nlm:aff id="A6">Lead Contact</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31722203</idno><idno type="pmc">6886713</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886713</idno><idno type="RBID">PMC:6886713</idno><idno type="doi">10.1016/j.celrep.2019.10.032</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000854</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000854</idno><idno type="wicri:Area/Pmc/Curation">000854</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000854</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">NIX-Mediated Mitophagy Promotes Effector Memory Formation in Antigen-Specific CD8<sup>+</sup> T Cells</title><author><name sortKey="Gupta, Shubhranshu S" sort="Gupta, Shubhranshu S" uniqKey="Gupta S" first="Shubhranshu S." last="Gupta">Shubhranshu S. Gupta</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX 77030</wicri:regionArea></affiliation></author><author><name sortKey="Sharp, Robert" sort="Sharp, Robert" uniqKey="Sharp R" first="Robert" last="Sharp">Robert Sharp</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030</wicri:regionArea></affiliation></author><author><name sortKey="Hofferek, Colby" sort="Hofferek, Colby" uniqKey="Hofferek C" first="Colby" last="Hofferek">Colby Hofferek</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030</wicri:regionArea></affiliation></author><author><name sortKey="Kuai, Le" sort="Kuai, Le" uniqKey="Kuai L" first="Le" last="Kuai">Le Kuai</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030</wicri:regionArea></affiliation></author><author><name sortKey="Dorn, Gerald W" sort="Dorn, Gerald W" uniqKey="Dorn G" first="Gerald W." last="Dorn">Gerald W. Dorn</name><affiliation wicri:level="1"><nlm:aff id="A3">Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Jin" sort="Wang, Jin" uniqKey="Wang J" first="Jin" last="Wang">Jin Wang</name><affiliation wicri:level="1"><nlm:aff id="A4">Immunobiology and Transplant Science Center, Houston Methodist Research Institute, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Immunobiology and Transplant Science Center, Houston Methodist Research Institute, Houston, TX 77030</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A5">Department of Surgery, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery, Weill Cornell Medical College, Cornell University, New York, NY 10065</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Min" sort="Chen, Min" uniqKey="Chen M" first="Min" last="Chen">Min Chen</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX 77030</wicri:regionArea></affiliation><affiliation><nlm:aff id="A6">Lead Contact</nlm:aff></affiliation></author></analytic><series><title level="j">Cell reports</title><idno type="eISSN">2211-1247</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>SUMMARY</title><p id="P3">Autophagy plays a critical role in the maintenance of immunological memory. However, the molecular mechanisms involved in autophagy-regulated effector memory formation in CD8<sup>+</sup> T cells remain unclear. Here we show that deficiency in NIX-dependent mitophagy leads to metabolic defects in effector memory T cells. Deletion of NIX caused HIF1α accumulation and altered cellular metabolism from long-chain fatty acid to short/branched-chain fatty acid oxidation, thereby compromising ATP synthesis during effector memory formation. Preventing HIF1α accumulation restored long-chain fatty acid metabolism and effector memory formation in antigen-specific CD8<sup>+</sup> T cells. Our study suggests that NIX-mediated mitophagy is critical for effector memory formation in T cells.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Akondy, Rs" uniqKey="Akondy R">RS Akondy</name></author><author><name sortKey="Fitch, M" uniqKey="Fitch M">M Fitch</name></author><author><name sortKey="Edupuganti, S" uniqKey="Edupuganti S">S Edupuganti</name></author><author><name sortKey="Yang, S" uniqKey="Yang S">S Yang</name></author><author><name sortKey="Kissick, Ht" uniqKey="Kissick H">HT Kissick</name></author><author><name sortKey="Li, Kw" uniqKey="Li K">KW Li</name></author><author><name sortKey="Youngblood, Ba" uniqKey="Youngblood B">BA Youngblood</name></author><author><name sortKey="Abdelsamed, Ha" uniqKey="Abdelsamed H">HA Abdelsamed</name></author><author><name sortKey="Mcguire, Dj" uniqKey="Mcguire D">DJ McGuire</name></author><author><name sortKey="Cohen, Kw" uniqKey="Cohen K">KW Cohen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alfardan, J" uniqKey="Alfardan J">J Alfardan</name></author><author><name sortKey="Mohsen, A W" uniqKey="Mohsen A">A-W Mohsen</name></author><author><name sortKey="Copeland, S" uniqKey="Copeland S">S Copeland</name></author><author><name sortKey="Ellison, J" uniqKey="Ellison J">J Ellison</name></author><author><name sortKey="Keppen Davis, L" uniqKey="Keppen Davis L">L Keppen-Davis</name></author><author><name sortKey="Rohrbach, M" uniqKey="Rohrbach M">M Rohrbach</name></author><author><name sortKey="Powell, Br" uniqKey="Powell B">BR Powell</name></author><author><name sortKey="Gillis, J" uniqKey="Gillis J">J Gillis</name></author><author><name sortKey="Matern, D" uniqKey="Matern D">D Matern</name></author><author><name sortKey="Kant, J" uniqKey="Kant J">J Kant</name></author><author><name sortKey="Vockley, J" uniqKey="Vockley J">J Vockley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Almeida, L" uniqKey="Almeida L">L Almeida</name></author><author><name sortKey="Lochner, M" uniqKey="Lochner M">M Lochner</name></author><author><name sortKey="Berod, L" uniqKey="Berod L">L Berod</name></author><author><name sortKey="Sparwasser, T" uniqKey="Sparwasser T">T Sparwasser</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Araujo, Lf" uniqKey="Araujo L">LF Araujo</name></author><author><name sortKey="Siena, Add" uniqKey="Siena A">ADD Siena</name></author><author><name sortKey="Placa, Jr" uniqKey="Placa J">JR Plaça</name></author><author><name sortKey="Brotto, Db" uniqKey="Brotto D">DB Brotto</name></author><author><name sortKey="Barros, Ii" uniqKey="Barros I">II Barros</name></author><author><name sortKey="Muys, Br" uniqKey="Muys B">BR Muys</name></author><author><name sortKey="Biagi, Cao" uniqKey="Biagi C">CAO Biagi</name></author><author><name sortKey="Peronni, Kc" uniqKey="Peronni K">KC Peronni</name></author><author><name sortKey="Sousa, Jf" uniqKey="Sousa J">JF Sousa</name></author><author><name sortKey="Molfetta, Ga" uniqKey="Molfetta G">GA Molfetta</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Avery, L" uniqKey="Avery L">L Avery</name></author><author><name sortKey="Filderman, J" uniqKey="Filderman J">J Filderman</name></author><author><name sortKey="Szymczak Workman, Al" uniqKey="Szymczak Workman A">AL Szymczak-Workman</name></author><author><name sortKey="Kane, Lp" uniqKey="Kane L">LP Kane</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baixauli, F" uniqKey="Baixauli F">F Baixauli</name></author><author><name sortKey="Martin C Freces, Nb" uniqKey="Martin C Freces N">NB Martín-Cófreces</name></author><author><name sortKey="Morlino, G" uniqKey="Morlino G">G Morlino</name></author><author><name sortKey="Carrasco, Yr" uniqKey="Carrasco Y">YR Carrasco</name></author><author><name sortKey="Calabia Linares, C" uniqKey="Calabia Linares C">C Calabia-Linares</name></author><author><name sortKey="Veiga, E" uniqKey="Veiga E">E Veiga</name></author><author><name sortKey="Serrador, Jm" uniqKey="Serrador J">JM Serrador</name></author><author><name sortKey="Sanchez Madrid, F" uniqKey="Sanchez Madrid F">F Sánchez-Madrid</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beckermann, Ke" uniqKey="Beckermann K">KE Beckermann</name></author><author><name sortKey="Dudzinski, So" uniqKey="Dudzinski S">SO Dudzinski</name></author><author><name sortKey="Rathmell, Jc" uniqKey="Rathmell J">JC Rathmell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beckhove, P" uniqKey="Beckhove P">P Beckhove</name></author><author><name sortKey="Feuerer, M" uniqKey="Feuerer M">M Feuerer</name></author><author><name sortKey="Dolenc, M" uniqKey="Dolenc M">M Dolenc</name></author><author><name sortKey="Schuetz, F" uniqKey="Schuetz F">F Schuetz</name></author><author><name sortKey="Choi, C" uniqKey="Choi C">C Choi</name></author><author><name sortKey="Sommerfeldt, N" uniqKey="Sommerfeldt N">N Sommerfeldt</name></author><author><name sortKey="Schwendemann, J" uniqKey="Schwendemann J">J Schwendemann</name></author><author><name sortKey="Ehlert, K" uniqKey="Ehlert K">K Ehlert</name></author><author><name sortKey="Altevogt, P" uniqKey="Altevogt P">P Altevogt</name></author><author><name sortKey="Bastert, G" uniqKey="Bastert G">G Bastert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beeton, C" uniqKey="Beeton C">C Beeton</name></author><author><name sortKey="Pennington, Mw" uniqKey="Pennington M">MW Pennington</name></author><author><name sortKey="Wulff, H" uniqKey="Wulff H">H Wulff</name></author><author><name sortKey="Singh, S" uniqKey="Singh S">S Singh</name></author><author><name sortKey="Nugent, D" uniqKey="Nugent D">D Nugent</name></author><author><name sortKey="Crossley, G" uniqKey="Crossley G">G Crossley</name></author><author><name sortKey="Khaytin, I" uniqKey="Khaytin I">I Khaytin</name></author><author><name sortKey="Calabresi, Pa" uniqKey="Calabresi P">PA Calabresi</name></author><author><name sortKey="Chen, Cy" uniqKey="Chen C">CY Chen</name></author><author><name sortKey="Gutman, Ga" uniqKey="Gutman G">GA Gutman</name></author><author><name sortKey="Chandy, Kg" uniqKey="Chandy K">KG Chandy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beeton, C" uniqKey="Beeton C">C Beeton</name></author><author><name sortKey="Wulff, H" uniqKey="Wulff H">H Wulff</name></author><author><name sortKey="Standifer, Ne" uniqKey="Standifer N">NE Standifer</name></author><author><name sortKey="Azam, P" uniqKey="Azam P">P Azam</name></author><author><name sortKey="Mullen, Km" uniqKey="Mullen K">KM Mullen</name></author><author><name sortKey="Pennington, Mw" uniqKey="Pennington M">MW Pennington</name></author><author><name sortKey="Kolski Andreaco, A" uniqKey="Kolski Andreaco A">A Kolski-Andreaco</name></author><author><name sortKey="Wei, E" uniqKey="Wei E">E Wei</name></author><author><name sortKey="Grino, A" uniqKey="Grino A">A Grino</name></author><author><name sortKey="Counts, Dr" uniqKey="Counts D">DR Counts</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bengsch, B" uniqKey="Bengsch B">B Bengsch</name></author><author><name sortKey="Spangenberg, Hc" uniqKey="Spangenberg H">HC Spangenberg</name></author><author><name sortKey="Kersting, N" uniqKey="Kersting N">N Kersting</name></author><author><name sortKey="Neumann Haefelin, C" uniqKey="Neumann Haefelin C">C Neumann-Haefelin</name></author><author><name sortKey="Panther, E" uniqKey="Panther E">E Panther</name></author><author><name sortKey="Von Weizs Cker, F" uniqKey="Von Weizs Cker F">F von Weizsäcker</name></author><author><name sortKey="Blum, He" uniqKey="Blum H">HE Blum</name></author><author><name sortKey="Pircher, H" uniqKey="Pircher H">H Pircher</name></author><author><name sortKey="Thimme, R" uniqKey="Thimme R">R Thimme</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bhargava, P" uniqKey="Bhargava P">P Bhargava</name></author><author><name sortKey="Calabresi, Pa" uniqKey="Calabresi P">PA Calabresi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bian, M" uniqKey="Bian M">M Bian</name></author><author><name sortKey="Liu, J" uniqKey="Liu J">J Liu</name></author><author><name sortKey="Hong, X" uniqKey="Hong X">X Hong</name></author><author><name sortKey="Yu, M" uniqKey="Yu M">M Yu</name></author><author><name sortKey="Huang, Y" uniqKey="Huang Y">Y Huang</name></author><author><name sortKey="Sheng, Z" uniqKey="Sheng Z">Z Sheng</name></author><author><name sortKey="Fei, J" uniqKey="Fei J">J Fei</name></author><author><name sortKey="Huang, F" uniqKey="Huang F">F Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Billingsley, Jm" uniqKey="Billingsley J">JM Billingsley</name></author><author><name sortKey="Rajakumar, Pa" uniqKey="Rajakumar P">PA Rajakumar</name></author><author><name sortKey="Connole, Ma" uniqKey="Connole M">MA Connole</name></author><author><name sortKey="Salisch, Nc" uniqKey="Salisch N">NC Salisch</name></author><author><name sortKey="Adnan, S" uniqKey="Adnan S">S Adnan</name></author><author><name sortKey="Kuzmichev, Yv" uniqKey="Kuzmichev Y">YV Kuzmichev</name></author><author><name sortKey="Hong, Hs" uniqKey="Hong H">HS Hong</name></author><author><name sortKey="Reeves, Rk" uniqKey="Reeves R">RK Reeves</name></author><author><name sortKey="Kang, H J" uniqKey="Kang H">H-J Kang</name></author><author><name sortKey="Li, W" uniqKey="Li W">W Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bordi, M" uniqKey="Bordi M">M Bordi</name></author><author><name sortKey="Nazio, F" uniqKey="Nazio F">F Nazio</name></author><author><name sortKey="Campello, S" uniqKey="Campello S">S Campello</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Buck, Mdd" uniqKey="Buck M">MDD Buck</name></author><author><name sortKey="O Ullivan, D" uniqKey="O Ullivan D">D O’Sullivan</name></author><author><name sortKey="Klein Geltink, Ri" uniqKey="Klein Geltink R">RI Klein Geltink</name></author><author><name sortKey="Curtis, Jd" uniqKey="Curtis J">JD Curtis</name></author><author><name sortKey="Chang, Ch" uniqKey="Chang C">CH Chang</name></author><author><name sortKey="Sanin, De" uniqKey="Sanin D">DE Sanin</name></author><author><name sortKey="Qiu, J" uniqKey="Qiu J">J Qiu</name></author><author><name sortKey="Kretz, O" uniqKey="Kretz O">O Kretz</name></author><author><name sortKey="Braas, D" uniqKey="Braas D">D Braas</name></author><author><name sortKey="Van Der Windt, Gj" uniqKey="Van Der Windt G">GJ van der Windt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carracedo, A" uniqKey="Carracedo A">A Carracedo</name></author><author><name sortKey="Cantley, Lc" uniqKey="Cantley L">LC Cantley</name></author><author><name sortKey="Pandolfi, Pp" uniqKey="Pandolfi P">PP Pandolfi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chandel, Ns" uniqKey="Chandel N">NS Chandel</name></author><author><name sortKey="Maltepe, E" uniqKey="Maltepe E">E Maltepe</name></author><author><name sortKey="Goldwasser, E" uniqKey="Goldwasser E">E Goldwasser</name></author><author><name sortKey="Mathieu, Ce" uniqKey="Mathieu C">CE Mathieu</name></author><author><name sortKey="Simon, Mc" uniqKey="Simon M">MC Simon</name></author><author><name sortKey="Schumacker, Pt" uniqKey="Schumacker P">PT Schumacker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chandel, Ns" uniqKey="Chandel N">NS Chandel</name></author><author><name sortKey="Mcclintock, Ds" uniqKey="Mcclintock D">DS McClintock</name></author><author><name sortKey="Feliciano, Ce" uniqKey="Feliciano C">CE Feliciano</name></author><author><name sortKey="Wood, Tm" uniqKey="Wood T">TM Wood</name></author><author><name sortKey="Melendez, Ja" uniqKey="Melendez J">JA Melendez</name></author><author><name sortKey="Rodriguez, Am" uniqKey="Rodriguez A">AM Rodriguez</name></author><author><name sortKey="Schumacker, Pt" uniqKey="Schumacker P">PT Schumacker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chee, J" uniqKey="Chee J">J Chee</name></author><author><name sortKey="Ko, Hj" uniqKey="Ko H">HJ Ko</name></author><author><name sortKey="Skowera, A" uniqKey="Skowera A">A Skowera</name></author><author><name sortKey="Jhala, G" uniqKey="Jhala G">G Jhala</name></author><author><name sortKey="Catterall, T" uniqKey="Catterall T">T Catterall</name></author><author><name sortKey="Graham, Kl" uniqKey="Graham K">KL Graham</name></author><author><name sortKey="Sutherland, Rm" uniqKey="Sutherland R">RM Sutherland</name></author><author><name sortKey="Thomas, He" uniqKey="Thomas H">HE Thomas</name></author><author><name sortKey="Lew, Am" uniqKey="Lew A">AM Lew</name></author><author><name sortKey="Peakman, M" uniqKey="Peakman M">M Peakman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, M" uniqKey="Chen M">M Chen</name></author><author><name sortKey="Wang, Yh" uniqKey="Wang Y">YH Wang</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name></author><author><name sortKey="Huang, L" uniqKey="Huang L">L Huang</name></author><author><name sortKey="Sandoval, H" uniqKey="Sandoval H">H Sandoval</name></author><author><name sortKey="Liu, Yj" uniqKey="Liu Y">YJ Liu</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, M" uniqKey="Chen M">M Chen</name></author><author><name sortKey="Hong, Mj" uniqKey="Hong M">MJ Hong</name></author><author><name sortKey="Sun, H" uniqKey="Sun H">H Sun</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author><author><name sortKey="Shi, X" uniqKey="Shi X">X Shi</name></author><author><name sortKey="Gilbert, Be" uniqKey="Gilbert B">BE Gilbert</name></author><author><name sortKey="Corry, Db" uniqKey="Corry D">DB Corry</name></author><author><name sortKey="Kheradmand, F" uniqKey="Kheradmand F">F Kheradmand</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, M" uniqKey="Chen M">M Chen</name></author><author><name sortKey="Kodali, S" uniqKey="Kodali S">S Kodali</name></author><author><name sortKey="Jang, A" uniqKey="Jang A">A Jang</name></author><author><name sortKey="Kuai, L" uniqKey="Kuai L">L Kuai</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chirichigno, Jw" uniqKey="Chirichigno J">JW Chirichigno</name></author><author><name sortKey="Manfredi, G" uniqKey="Manfredi G">G Manfredi</name></author><author><name sortKey="Beal, Mf" uniqKey="Beal M">MF Beal</name></author><author><name sortKey="Albers, Ds" uniqKey="Albers D">DS Albers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cole, Jt" uniqKey="Cole J">JT Cole</name></author><author><name sortKey="Rajendram, R" uniqKey="Rajendram R">R Rajendram</name></author><author><name sortKey="Preedy, Vr" uniqKey="Preedy V">VR Preedy</name></author><author><name sortKey="Patel, V" uniqKey="Patel V">V Patel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="D Ouza, Wn" uniqKey="D Ouza W">WN D’Souza</name></author><author><name sortKey="Hedrick, Sm" uniqKey="Hedrick S">SM Hedrick</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Danilo, M" uniqKey="Danilo M">M Danilo</name></author><author><name sortKey="Chennupati, V" uniqKey="Chennupati V">V Chennupati</name></author><author><name sortKey="Silva, Jg" uniqKey="Silva J">JG Silva</name></author><author><name sortKey="Siegert, S" uniqKey="Siegert S">S Siegert</name></author><author><name sortKey="Held, W" uniqKey="Held W">W Held</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Den Besten, G" uniqKey="Den Besten G">G den Besten</name></author><author><name sortKey="Van Eunen, K" uniqKey="Van Eunen K">K van Eunen</name></author><author><name sortKey="Groen, Ak" uniqKey="Groen A">AK Groen</name></author><author><name sortKey="Venema, K" uniqKey="Venema K">K Venema</name></author><author><name sortKey="Reijngoud, Dj" uniqKey="Reijngoud D">DJ Reijngoud</name></author><author><name sortKey="Bakker, Bm" uniqKey="Bakker B">BM Bakker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Desdin Mico, G" uniqKey="Desdin Mico G">G Desdin-Mico</name></author><author><name sortKey="Soto Heredero, G" uniqKey="Soto Heredero G">G Soto-Heredero</name></author><author><name sortKey="Mittelbrunn, M" uniqKey="Mittelbrunn M">M Mittelbrunn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Diwan, A" uniqKey="Diwan A">A Diwan</name></author><author><name sortKey="Koesters, Ag" uniqKey="Koesters A">AG Koesters</name></author><author><name sortKey="Odley, Am" uniqKey="Odley A">AM Odley</name></author><author><name sortKey="Pushkaran, S" uniqKey="Pushkaran S">S Pushkaran</name></author><author><name sortKey="Baines, Cp" uniqKey="Baines C">CP Baines</name></author><author><name sortKey="Spike, Bt" uniqKey="Spike B">BT Spike</name></author><author><name sortKey="Daria, D" uniqKey="Daria D">D Daria</name></author><author><name sortKey="Jegga, Ag" uniqKey="Jegga A">AG Jegga</name></author><author><name sortKey="Geiger, H" uniqKey="Geiger H">H Geiger</name></author><author><name sortKey="Aronow, Bj" uniqKey="Aronow B">BJ Aronow</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ellis, Gi" uniqKey="Ellis G">GI Ellis</name></author><author><name sortKey="Zhi, L" uniqKey="Zhi L">L Zhi</name></author><author><name sortKey="Akundi, R" uniqKey="Akundi R">R Akundi</name></author><author><name sortKey="Bueler, H" uniqKey="Bueler H">H Büeler</name></author><author><name sortKey="Marti, F" uniqKey="Marti F">F Marti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ganeshan, K" uniqKey="Ganeshan K">K Ganeshan</name></author><author><name sortKey="Chawla, A" uniqKey="Chawla A">A Chawla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Garrod, Kr" uniqKey="Garrod K">KR Garrod</name></author><author><name sortKey="Moreau, Hd" uniqKey="Moreau H">HD Moreau</name></author><author><name sortKey="Garcia, Z" uniqKey="Garcia Z">Z Garcia</name></author><author><name sortKey="Lemaitre, F" uniqKey="Lemaitre F">F Lemaître</name></author><author><name sortKey="Bouvier, I" uniqKey="Bouvier I">I Bouvier</name></author><author><name sortKey="Albert, Ml" uniqKey="Albert M">ML Albert</name></author><author><name sortKey="Bousso, P" uniqKey="Bousso P">P Bousso</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gkikas, I" uniqKey="Gkikas I">I Gkikas</name></author><author><name sortKey="Palikaras, K" uniqKey="Palikaras K">K Palikaras</name></author><author><name sortKey="Tavernarakis, N" uniqKey="Tavernarakis N">N Tavernarakis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gladkova, C" uniqKey="Gladkova C">C Gladkova</name></author><author><name sortKey="Maslen, Sl" uniqKey="Maslen S">SL Maslen</name></author><author><name sortKey="Skehel, Jm" uniqKey="Skehel J">JM Skehel</name></author><author><name sortKey="Komander, D" uniqKey="Komander D">D Komander</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Harrington, Le" uniqKey="Harrington L">LE Harrington</name></author><author><name sortKey="Galvan, M" uniqKey="Galvan M">M Galvan</name></author><author><name sortKey="Baum, Lg" uniqKey="Baum L">LG Baum</name></author><author><name sortKey="Altman, Jd" uniqKey="Altman J">JD Altman</name></author><author><name sortKey="Ahmed, R" uniqKey="Ahmed R">R Ahmed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Harris, Ra" uniqKey="Harris R">RA Harris</name></author><author><name sortKey="Paxton, R" uniqKey="Paxton R">R Paxton</name></author><author><name sortKey="Powell, Sm" uniqKey="Powell S">SM Powell</name></author><author><name sortKey="Goodwin, Gw" uniqKey="Goodwin G">GW Goodwin</name></author><author><name sortKey="Kuntz, Mj" uniqKey="Kuntz M">MJ Kuntz</name></author><author><name sortKey="Han, Ac" uniqKey="Han A">AC Han</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hashimoto, S" uniqKey="Hashimoto S">S Hashimoto</name></author><author><name sortKey="Ogoshi, K" uniqKey="Ogoshi K">K Ogoshi</name></author><author><name sortKey="Sasaki, A" uniqKey="Sasaki A">A Sasaki</name></author><author><name sortKey="Abe, J" uniqKey="Abe J">J Abe</name></author><author><name sortKey="Qu, W" uniqKey="Qu W">W Qu</name></author><author><name sortKey="Nakatani, Y" uniqKey="Nakatani Y">Y Nakatani</name></author><author><name sortKey="Ahsan, B" uniqKey="Ahsan B">B Ahsan</name></author><author><name sortKey="Oshima, K" uniqKey="Oshima K">K Oshima</name></author><author><name sortKey="Shand, Fhw" uniqKey="Shand F">FHW Shand</name></author><author><name sortKey="Ametani, A" uniqKey="Ametani A">A Ametani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Herst, Pm" uniqKey="Herst P">PM Herst</name></author><author><name sortKey="Rowe, Mr" uniqKey="Rowe M">MR Rowe</name></author><author><name sortKey="Carson, Gm" uniqKey="Carson G">GM Carson</name></author><author><name sortKey="Berridge, Mv" uniqKey="Berridge M">MV Berridge</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hess Michelini, R" uniqKey="Hess Michelini R">R Hess Michelini</name></author><author><name sortKey="Doedens, Al" uniqKey="Doedens A">AL Doedens</name></author><author><name sortKey="Goldrath, Aw" uniqKey="Goldrath A">AW Goldrath</name></author><author><name sortKey="Hedrick, Sm" uniqKey="Hedrick S">SM Hedrick</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hikono, H" uniqKey="Hikono H">H Hikono</name></author><author><name sortKey="Kohlmeier, Je" uniqKey="Kohlmeier J">JE Kohlmeier</name></author><author><name sortKey="Takamura, S" uniqKey="Takamura S">S Takamura</name></author><author><name sortKey="Wittmer, St" uniqKey="Wittmer S">ST Wittmer</name></author><author><name sortKey="Roberts, Ad" uniqKey="Roberts A">AD Roberts</name></author><author><name sortKey="Woodland, Dl" uniqKey="Woodland D">DL Woodland</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hu, G" uniqKey="Hu G">G Hu</name></author><author><name sortKey="Wang, S" uniqKey="Wang S">S Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jezek, J" uniqKey="Jezek J">J Ježek</name></author><author><name sortKey="Cooper, Kf" uniqKey="Cooper K">KF Cooper</name></author><author><name sortKey="Strich, R" uniqKey="Strich R">R Strich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jia, Z" uniqKey="Jia Z">Z Jia</name></author><author><name sortKey="Moulson, Cl" uniqKey="Moulson C">CL Moulson</name></author><author><name sortKey="Pei, Z" uniqKey="Pei Z">Z Pei</name></author><author><name sortKey="Miner, Jh" uniqKey="Miner J">JH Miner</name></author><author><name sortKey="Watkins, Pa" uniqKey="Watkins P">PA Watkins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jiang, P" uniqKey="Jiang P">P Jiang</name></author><author><name sortKey="Fang, X" uniqKey="Fang X">X Fang</name></author><author><name sortKey="Zhao, Z" uniqKey="Zhao Z">Z Zhao</name></author><author><name sortKey="Yu, X" uniqKey="Yu X">X Yu</name></author><author><name sortKey="Sun, B" uniqKey="Sun B">B Sun</name></author><author><name sortKey="Yu, H" uniqKey="Yu H">H Yu</name></author><author><name sortKey="Yang, R" uniqKey="Yang R">R Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jin, Sm" uniqKey="Jin S">SM Jin</name></author><author><name sortKey="Youle, Rj" uniqKey="Youle R">RJ Youle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jornayvaz, Fr" uniqKey="Jornayvaz F">FR Jornayvaz</name></author><author><name sortKey="Shulman, Gig" uniqKey="Shulman G">GIG Shulman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Joshi, Ns" uniqKey="Joshi N">NS Joshi</name></author><author><name sortKey="Cui, W" uniqKey="Cui W">W Cui</name></author><author><name sortKey="Chandele, A" uniqKey="Chandele A">A Chandele</name></author><author><name sortKey="Lee, Hk" uniqKey="Lee H">HK Lee</name></author><author><name sortKey="Urso, Dr" uniqKey="Urso D">DR Urso</name></author><author><name sortKey="Hagman, J" uniqKey="Hagman J">J Hagman</name></author><author><name sortKey="Gapin, L" uniqKey="Gapin L">L Gapin</name></author><author><name sortKey="Kaech, Sm" uniqKey="Kaech S">SM Kaech</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kaech, Sm" uniqKey="Kaech S">SM Kaech</name></author><author><name sortKey="Ahmed, R" uniqKey="Ahmed R">R Ahmed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kaech, Sm" uniqKey="Kaech S">SM Kaech</name></author><author><name sortKey="Cui, W" uniqKey="Cui W">W Cui</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kaminski, Mm" uniqKey="Kaminski M">MM Kaminski</name></author><author><name sortKey="Sauer, Sw" uniqKey="Sauer S">SW Sauer</name></author><author><name sortKey="Klemke, Cd" uniqKey="Klemke C">CD Klemke</name></author><author><name sortKey="Suss, D" uniqKey="Suss D">D Süss</name></author><author><name sortKey="Okun, Jg" uniqKey="Okun J">JG Okun</name></author><author><name sortKey="Krammer, Ph" uniqKey="Krammer P">PH Krammer</name></author><author><name sortKey="Gulow, K" uniqKey="Gulow K">K Gülow</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kang, D" uniqKey="Kang D">D Kang</name></author><author><name sortKey="Hamasaki, N" uniqKey="Hamasaki N">N Hamasaki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kapoor, Vn" uniqKey="Kapoor V">VN Kapoor</name></author><author><name sortKey="Shin, Hm" uniqKey="Shin H">HM Shin</name></author><author><name sortKey="Cho, Oh" uniqKey="Cho O">OH Cho</name></author><author><name sortKey="Berg, Lj" uniqKey="Berg L">LJ Berg</name></author><author><name sortKey="Kang, J" uniqKey="Kang J">J Kang</name></author><author><name sortKey="Welsh, Rm" uniqKey="Welsh R">RM Welsh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Mv" uniqKey="Kim M">MV Kim</name></author><author><name sortKey="Ouyang, W" uniqKey="Ouyang W">W Ouyang</name></author><author><name sortKey="Liao, W" uniqKey="Liao W">W Liao</name></author><author><name sortKey="Zhang, Mq" uniqKey="Zhang M">MQ Zhang</name></author><author><name sortKey="Li, Mo" uniqKey="Li M">MO Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kurtz, Dm" uniqKey="Kurtz D">DM Kurtz</name></author><author><name sortKey="Rinaldo, P" uniqKey="Rinaldo P">P Rinaldo</name></author><author><name sortKey="Rhead, Wj" uniqKey="Rhead W">WJ Rhead</name></author><author><name sortKey="Tian, L" uniqKey="Tian L">L Tian</name></author><author><name sortKey="Millington, Ds" uniqKey="Millington D">DS Millington</name></author><author><name sortKey="Vockley, J" uniqKey="Vockley J">J Vockley</name></author><author><name sortKey="Hamm, Da" uniqKey="Hamm D">DA Hamm</name></author><author><name sortKey="Brix, Ae" uniqKey="Brix A">AE Brix</name></author><author><name sortKey="Lindsey, Jr" uniqKey="Lindsey J">JR Lindsey</name></author><author><name sortKey="Pinkert, Ca" uniqKey="Pinkert C">CA Pinkert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lauvau, G" uniqKey="Lauvau G">G Lauvau</name></author><author><name sortKey="Soudja, Sm" uniqKey="Soudja S">SM Soudja</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, Ke" uniqKey="Lee K">KE Lee</name></author><author><name sortKey="Simon, Mc" uniqKey="Simon M">MC Simon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, K" uniqKey="Lee K">K Lee</name></author><author><name sortKey="Lee, Jh" uniqKey="Lee J">JH Lee</name></author><author><name sortKey="Boovanahalli, Sk" uniqKey="Boovanahalli S">SK Boovanahalli</name></author><author><name sortKey="Jin, Y" uniqKey="Jin Y">Y Jin</name></author><author><name sortKey="Lee, M" uniqKey="Lee M">M Lee</name></author><author><name sortKey="Jin, X" uniqKey="Jin X">X Jin</name></author><author><name sortKey="Kim, Jh" uniqKey="Kim J">JH Kim</name></author><author><name sortKey="Hong, Ys" uniqKey="Hong Y">YS Hong</name></author><author><name sortKey="Lee, Jj" uniqKey="Lee J">JJ Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leong, Ya" uniqKey="Leong Y">YA Leong</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name></author><author><name sortKey="Ong, Hs" uniqKey="Ong H">HS Ong</name></author><author><name sortKey="Wu, D" uniqKey="Wu D">D Wu</name></author><author><name sortKey="Man, K" uniqKey="Man K">K Man</name></author><author><name sortKey="Deleage, C" uniqKey="Deleage C">C Deleage</name></author><author><name sortKey="Minnich, M" uniqKey="Minnich M">M Minnich</name></author><author><name sortKey="Meckiff, Bj" uniqKey="Meckiff B">BJ Meckiff</name></author><author><name sortKey="Wei, Y" uniqKey="Wei Y">Y Wei</name></author><author><name sortKey="Hou, Z" uniqKey="Hou Z">Z Hou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, J" uniqKey="Li J">J Li</name></author><author><name sortKey="Ma, C" uniqKey="Ma C">C Ma</name></author><author><name sortKey="Long, F" uniqKey="Long F">F Long</name></author><author><name sortKey="Yang, D" uniqKey="Yang D">D Yang</name></author><author><name sortKey="Liu, X" uniqKey="Liu X">X Liu</name></author><author><name sortKey="Hu, Y" uniqKey="Hu Y">Y Hu</name></author><author><name sortKey="Wu, C" uniqKey="Wu C">C Wu</name></author><author><name sortKey="Wang, B" uniqKey="Wang B">B Wang</name></author><author><name sortKey="Wang, M" uniqKey="Wang M">M Wang</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, Ww" uniqKey="Lin W">WW Lin</name></author><author><name sortKey="Nish, Sa" uniqKey="Nish S">SA Nish</name></author><author><name sortKey="Yen, B" uniqKey="Yen B">B Yen</name></author><author><name sortKey="Chen, Yh" uniqKey="Chen Y">YH Chen</name></author><author><name sortKey="Adams, Wc" uniqKey="Adams W">WC Adams</name></author><author><name sortKey="Kratchmarov, R" uniqKey="Kratchmarov R">R Kratchmarov</name></author><author><name sortKey="Rothman, Nj" uniqKey="Rothman N">NJ Rothman</name></author><author><name sortKey="Bhandoola, A" uniqKey="Bhandoola A">A Bhandoola</name></author><author><name sortKey="Xue, Hh" uniqKey="Xue H">HH Xue</name></author><author><name sortKey="Reiner, Sl" uniqKey="Reiner S">SL Reiner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, L" uniqKey="Liu L">L Liu</name></author><author><name sortKey="Feng, D" uniqKey="Feng D">D Feng</name></author><author><name sortKey="Chen, G" uniqKey="Chen G">G Chen</name></author><author><name sortKey="Chen, M" uniqKey="Chen M">M Chen</name></author><author><name sortKey="Zheng, Q" uniqKey="Zheng Q">Q Zheng</name></author><author><name sortKey="Song, P" uniqKey="Song P">P Song</name></author><author><name sortKey="Ma, Q" uniqKey="Ma Q">Q Ma</name></author><author><name sortKey="Zhu, C" uniqKey="Zhu C">C Zhu</name></author><author><name sortKey="Wang, R" uniqKey="Wang R">R Wang</name></author><author><name sortKey="Qi, W" uniqKey="Qi W">W Qi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Luis, Pbm" uniqKey="Luis P">PBM Luís</name></author><author><name sortKey="Ruiter, Jpn" uniqKey="Ruiter J">JPN Ruiter</name></author><author><name sortKey="Ijlst, L" uniqKey="Ijlst L">L Ijlst</name></author><author><name sortKey="Tavares De Almeida, I" uniqKey="Tavares De Almeida I">I Tavares de Almeida</name></author><author><name sortKey="Duran, M" uniqKey="Duran M">M Duran</name></author><author><name sortKey="Mohsen, Aw" uniqKey="Mohsen A">AW Mohsen</name></author><author><name sortKey="Vockley, J" uniqKey="Vockley J">J Vockley</name></author><author><name sortKey="Wanders, Rj" uniqKey="Wanders R">RJ Wanders</name></author><author><name sortKey="Silva, Mf" uniqKey="Silva M">MF Silva</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Masopust, D" uniqKey="Masopust D">D Masopust</name></author><author><name sortKey="Vezys, V" uniqKey="Vezys V">V Vezys</name></author><author><name sortKey="Marzo, Al" uniqKey="Marzo A">AL Marzo</name></author><author><name sortKey="Lefrancois, L" uniqKey="Lefrancois L">L Lefrançois</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matheoud, D" uniqKey="Matheoud D">D Matheoud</name></author><author><name sortKey="Cannon, T" uniqKey="Cannon T">T Cannon</name></author><author><name sortKey="Voisin, A" uniqKey="Voisin A">A Voisin</name></author><author><name sortKey="Penttinen, A M" uniqKey="Penttinen A">A-M Penttinen</name></author><author><name sortKey="Ramet, L" uniqKey="Ramet L">L Ramet</name></author><author><name sortKey="Fahmy, Am" uniqKey="Fahmy A">AM Fahmy</name></author><author><name sortKey="Ducrot, C" uniqKey="Ducrot C">C Ducrot</name></author><author><name sortKey="Laplante, A" uniqKey="Laplante A">A Laplante</name></author><author><name sortKey="Bourque, M J" uniqKey="Bourque M">M-J Bourque</name></author><author><name sortKey="Zhu, L" uniqKey="Zhu L">L Zhu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matheu, Mp" uniqKey="Matheu M">MP Matheu</name></author><author><name sortKey="Beeton, C" uniqKey="Beeton C">C Beeton</name></author><author><name sortKey="Garcia, A" uniqKey="Garcia A">A Garcia</name></author><author><name sortKey="Chi, V" uniqKey="Chi V">V Chi</name></author><author><name sortKey="Rangaraju, S" uniqKey="Rangaraju S">S Rangaraju</name></author><author><name sortKey="Safrina, O" uniqKey="Safrina O">O Safrina</name></author><author><name sortKey="Monaghan, K" uniqKey="Monaghan K">K Monaghan</name></author><author><name sortKey="Uemura, Mi" uniqKey="Uemura M">MI Uemura</name></author><author><name sortKey="Li, D" uniqKey="Li D">D Li</name></author><author><name sortKey="Pal, S" uniqKey="Pal S">S Pal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matsushima, M" uniqKey="Matsushima M">M Matsushima</name></author><author><name sortKey="Fujiwara, T" uniqKey="Fujiwara T">T Fujiwara</name></author><author><name sortKey="Takahashi, E" uniqKey="Takahashi E">E Takahashi</name></author><author><name sortKey="Minaguchi, T" uniqKey="Minaguchi T">T Minaguchi</name></author><author><name sortKey="Eguchi, Y" uniqKey="Eguchi Y">Y Eguchi</name></author><author><name sortKey="Tsujimoto, Y" uniqKey="Tsujimoto Y">Y Tsujimoto</name></author><author><name sortKey="Suzumori, K" uniqKey="Suzumori K">K Suzumori</name></author><author><name sortKey="Nakamura, Y" uniqKey="Nakamura Y">Y Nakamura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcnamee, En" uniqKey="Mcnamee E">EN McNamee</name></author><author><name sortKey="Korns Johnson, D" uniqKey="Korns Johnson D">D Korns Johnson</name></author><author><name sortKey="Homann, D" uniqKey="Homann D">D Homann</name></author><author><name sortKey="Clambey, Et" uniqKey="Clambey E">ET Clambey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Menk, Av" uniqKey="Menk A">AV Menk</name></author><author><name sortKey="Scharping, Ne" uniqKey="Scharping N">NE Scharping</name></author><author><name sortKey="Moreci, Rs" uniqKey="Moreci R">RS Moreci</name></author><author><name sortKey="Zeng, X" uniqKey="Zeng X">X Zeng</name></author><author><name sortKey="Guy, C" uniqKey="Guy C">C Guy</name></author><author><name sortKey="Salvatore, S" uniqKey="Salvatore S">S Salvatore</name></author><author><name sortKey="Bae, H" uniqKey="Bae H">H Bae</name></author><author><name sortKey="Xie, J" uniqKey="Xie J">J Xie</name></author><author><name sortKey="Young, Ha" uniqKey="Young H">HA Young</name></author><author><name sortKey="Wendell, Sg" uniqKey="Wendell S">SG Wendell</name></author><author><name sortKey="Delgoffe, Gm" uniqKey="Delgoffe G">GM Delgoffe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Milner, Jj" uniqKey="Milner J">JJ Milner</name></author><author><name sortKey="Toma, C" uniqKey="Toma C">C Toma</name></author><author><name sortKey="Yu, B" uniqKey="Yu B">B Yu</name></author><author><name sortKey="Zhang, K" uniqKey="Zhang K">K Zhang</name></author><author><name sortKey="Omilusik, K" uniqKey="Omilusik K">K Omilusik</name></author><author><name sortKey="Phan, At" uniqKey="Phan A">AT Phan</name></author><author><name sortKey="Wang, D" uniqKey="Wang D">D Wang</name></author><author><name sortKey="Getzler, Aj" uniqKey="Getzler A">AJ Getzler</name></author><author><name sortKey="Nguyen, T" uniqKey="Nguyen T">T Nguyen</name></author><author><name sortKey="Crotty, S" uniqKey="Crotty S">S Crotty</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Murakawa, T" uniqKey="Murakawa T">T Murakawa</name></author><author><name sortKey="Yamaguchi, O" uniqKey="Yamaguchi O">O Yamaguchi</name></author><author><name sortKey="Hashimoto, A" uniqKey="Hashimoto A">A Hashimoto</name></author><author><name sortKey="Hikoso, S" uniqKey="Hikoso S">S Hikoso</name></author><author><name sortKey="Takeda, T" uniqKey="Takeda T">T Takeda</name></author><author><name sortKey="Oka, T" uniqKey="Oka T">T Oka</name></author><author><name sortKey="Yasui, H" uniqKey="Yasui H">H Yasui</name></author><author><name sortKey="Ueda, H" uniqKey="Ueda H">H Ueda</name></author><author><name sortKey="Akazawa, Y" uniqKey="Akazawa Y">Y Akazawa</name></author><author><name sortKey="Nakayama, H" uniqKey="Nakayama H">H Nakayama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Murera, D" uniqKey="Murera D">D Murera</name></author><author><name sortKey="Arbogast, F" uniqKey="Arbogast F">F Arbogast</name></author><author><name sortKey="Arnold, J" uniqKey="Arnold J">J Arnold</name></author><author><name sortKey="Bouis, D" uniqKey="Bouis D">D Bouis</name></author><author><name sortKey="Muller, S" uniqKey="Muller S">S Muller</name></author><author><name sortKey="Gros, F" uniqKey="Gros F">F Gros</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Murphy, Mp" uniqKey="Murphy M">MP Murphy</name></author><author><name sortKey="Siegel, Rm" uniqKey="Siegel R">RM Siegel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Obara, Y" uniqKey="Obara Y">Y Obara</name></author><author><name sortKey="Ishii, K" uniqKey="Ishii K">K Ishii</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="O Ullivan, D" uniqKey="O Ullivan D">D O’Sullivan</name></author><author><name sortKey="Van Der Windt, Gj" uniqKey="Van Der Windt G">GJ van der Windt</name></author><author><name sortKey="Huang, Sc" uniqKey="Huang S">SC Huang</name></author><author><name sortKey="Curtis, Jd" uniqKey="Curtis J">JD Curtis</name></author><author><name sortKey="Chang, Ch" uniqKey="Chang C">CH Chang</name></author><author><name sortKey="Buck, Md" uniqKey="Buck M">MD Buck</name></author><author><name sortKey="Qiu, J" uniqKey="Qiu J">J Qiu</name></author><author><name sortKey="Smith, Am" uniqKey="Smith A">AM Smith</name></author><author><name sortKey="Lam, Wy" uniqKey="Lam W">WY Lam</name></author><author><name sortKey="Diplato, Lm" uniqKey="Diplato L">LM DiPlato</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="O Ullivan, Te" uniqKey="O Ullivan T">TE O’Sullivan</name></author><author><name sortKey="Johnson, Lr" uniqKey="Johnson L">LR Johnson</name></author><author><name sortKey="Kang, Hh" uniqKey="Kang H">HH Kang</name></author><author><name sortKey="Sun, Jc" uniqKey="Sun J">JC Sun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Olson, Ja" uniqKey="Olson J">JA Olson</name></author><author><name sortKey="Mcdonald Hyman, C" uniqKey="Mcdonald Hyman C">C McDonald-Hyman</name></author><author><name sortKey="Jameson, Sc" uniqKey="Jameson S">SC Jameson</name></author><author><name sortKey="Hamilton, Se" uniqKey="Hamilton S">SE Hamilton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pike, Ls" uniqKey="Pike L">LS Pike</name></author><author><name sortKey="Smift, Al" uniqKey="Smift A">AL Smift</name></author><author><name sortKey="Croteau, Nj" uniqKey="Croteau N">NJ Croteau</name></author><author><name sortKey="Ferrick, Da" uniqKey="Ferrick D">DA Ferrick</name></author><author><name sortKey="Wu, M" uniqKey="Wu M">M Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pollizzi, Kn" uniqKey="Pollizzi K">KN Pollizzi</name></author><author><name sortKey="Powell, Jd" uniqKey="Powell J">JD Powell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Porter, Bb" uniqKey="Porter B">BB Porter</name></author><author><name sortKey="Harty, Jt" uniqKey="Harty J">JT Harty</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Puleston, Dj" uniqKey="Puleston D">DJ Puleston</name></author><author><name sortKey="Zhang, H" uniqKey="Zhang H">H Zhang</name></author><author><name sortKey="Powell, Tj" uniqKey="Powell T">TJ Powell</name></author><author><name sortKey="Lipina, E" uniqKey="Lipina E">E Lipina</name></author><author><name sortKey="Sims, S" uniqKey="Sims S">S Sims</name></author><author><name sortKey="Panse, I" uniqKey="Panse I">I Panse</name></author><author><name sortKey="Watson, As" uniqKey="Watson A">AS Watson</name></author><author><name sortKey="Cerundolo, V" uniqKey="Cerundolo V">V Cerundolo</name></author><author><name sortKey="Townsend, Ar" uniqKey="Townsend A">AR Townsend</name></author><author><name sortKey="Klenerman, P" uniqKey="Klenerman P">P Klenerman</name></author><author><name sortKey="Simon, Ak" uniqKey="Simon A">AK Simon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Putluri, N" uniqKey="Putluri N">N Putluri</name></author><author><name sortKey="Shojaie, A" uniqKey="Shojaie A">A Shojaie</name></author><author><name sortKey="Vasu, Vt" uniqKey="Vasu V">VT Vasu</name></author><author><name sortKey="Nalluri, S" uniqKey="Nalluri S">S Nalluri</name></author><author><name sortKey="Vareed, Sk" uniqKey="Vareed S">SK Vareed</name></author><author><name sortKey="Putluri, V" uniqKey="Putluri V">V Putluri</name></author><author><name sortKey="Vivekanandan Giri, A" uniqKey="Vivekanandan Giri A">A Vivekanandan-Giri</name></author><author><name sortKey="Byun, J" uniqKey="Byun J">J Byun</name></author><author><name sortKey="Pennathur, S" uniqKey="Pennathur S">S Pennathur</name></author><author><name sortKey="Sana, Tr" uniqKey="Sana T">TR Sana</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Putluri, N" uniqKey="Putluri N">N Putluri</name></author><author><name sortKey="Maity, S" uniqKey="Maity S">S Maity</name></author><author><name sortKey="Kommagani, R" uniqKey="Kommagani R">R Kommagani</name></author><author><name sortKey="Creighton, Cj" uniqKey="Creighton C">CJ Creighton</name></author><author><name sortKey="Putluri, V" uniqKey="Putluri V">V Putluri</name></author><author><name sortKey="Chen, F" uniqKey="Chen F">F Chen</name></author><author><name sortKey="Nanda, S" uniqKey="Nanda S">S Nanda</name></author><author><name sortKey="Bhowmik, Sk" uniqKey="Bhowmik S">SK Bhowmik</name></author><author><name sortKey="Terunuma, A" uniqKey="Terunuma A">A Terunuma</name></author><author><name sortKey="Dorsey, T" uniqKey="Dorsey T">T Dorsey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qu, A" uniqKey="Qu A">A Qu</name></author><author><name sortKey="Taylor, M" uniqKey="Taylor M">M Taylor</name></author><author><name sortKey="Xue, X" uniqKey="Xue X">X Xue</name></author><author><name sortKey="Matsubara, T" uniqKey="Matsubara T">T Matsubara</name></author><author><name sortKey="Metzger, D" uniqKey="Metzger D">D Metzger</name></author><author><name sortKey="Chambon, P" uniqKey="Chambon P">P Chambon</name></author><author><name sortKey="Gonzalez, Fj" uniqKey="Gonzalez F">FJ Gonzalez</name></author><author><name sortKey="Shah, Ym" uniqKey="Shah Y">YM Shah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Robbins, Sh" uniqKey="Robbins S">SH Robbins</name></author><author><name sortKey="Terrizzi, Sc" uniqKey="Terrizzi S">SC Terrizzi</name></author><author><name sortKey="Sydora, Bc" uniqKey="Sydora B">BC Sydora</name></author><author><name sortKey="Mikayama, T" uniqKey="Mikayama T">T Mikayama</name></author><author><name sortKey="Brossay, L" uniqKey="Brossay L">L Brossay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rodger, Ce" uniqKey="Rodger C">CE Rodger</name></author><author><name sortKey="Mcwilliams, Tg" uniqKey="Mcwilliams T">TG McWilliams</name></author><author><name sortKey="Ganley, Ig" uniqKey="Ganley I">IG Ganley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rutishauser, Rl" uniqKey="Rutishauser R">RL Rutishauser</name></author><author><name sortKey="Martins, Ga" uniqKey="Martins G">GA Martins</name></author><author><name sortKey="Kalachikov, S" uniqKey="Kalachikov S">S Kalachikov</name></author><author><name sortKey="Chandele, A" uniqKey="Chandele A">A Chandele</name></author><author><name sortKey="Parish, Ia" uniqKey="Parish I">IA Parish</name></author><author><name sortKey="Meffre, E" uniqKey="Meffre E">E Meffre</name></author><author><name sortKey="Jacob, J" uniqKey="Jacob J">J Jacob</name></author><author><name sortKey="Calame, K" uniqKey="Calame K">K Calame</name></author><author><name sortKey="Kaech, Sm" uniqKey="Kaech S">SM Kaech</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sabbagh, L" uniqKey="Sabbagh L">L Sabbagh</name></author><author><name sortKey="Kaech, Sm" uniqKey="Kaech S">SM Kaech</name></author><author><name sortKey="Bourbonniere, M" uniqKey="Bourbonniere M">M Bourbonnière</name></author><author><name sortKey="Woo, M" uniqKey="Woo M">M Woo</name></author><author><name sortKey="Cohen, Ly" uniqKey="Cohen L">LY Cohen</name></author><author><name sortKey="Haddad, Ek" uniqKey="Haddad E">EK Haddad</name></author><author><name sortKey="Labrecque, N" uniqKey="Labrecque N">N Labrecque</name></author><author><name sortKey="Ahmed, R" uniqKey="Ahmed R">R Ahmed</name></author><author><name sortKey="Sekaly, Rp" uniqKey="Sekaly R">RP Sékaly</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sabins, Nc" uniqKey="Sabins N">NC Sabins</name></author><author><name sortKey="Chornoguz, O" uniqKey="Chornoguz O">O Chornoguz</name></author><author><name sortKey="Leander, K" uniqKey="Leander K">K Leander</name></author><author><name sortKey="Kaplan, F" uniqKey="Kaplan F">F Kaplan</name></author><author><name sortKey="Carter, R" uniqKey="Carter R">R Carter</name></author><author><name sortKey="Kinder, M" uniqKey="Kinder M">M Kinder</name></author><author><name sortKey="Bachman, K" uniqKey="Bachman K">K Bachman</name></author><author><name sortKey="Verona, R" uniqKey="Verona R">R Verona</name></author><author><name sortKey="Shen, S" uniqKey="Shen S">S Shen</name></author><author><name sortKey="Bhargava, V" uniqKey="Bhargava V">V Bhargava</name></author><author><name sortKey="Santulli Marotto, S" uniqKey="Santulli Marotto S">S Santulli-Marotto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sallusto, F" uniqKey="Sallusto F">F Sallusto</name></author><author><name sortKey="Lenig, D" uniqKey="Lenig D">D Lenig</name></author><author><name sortKey="Forster, R" uniqKey="Forster R">R Förster</name></author><author><name sortKey="Lipp, M" uniqKey="Lipp M">M Lipp</name></author><author><name sortKey="Lanzavecchia, A" uniqKey="Lanzavecchia A">A Lanzavecchia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sallusto, F" uniqKey="Sallusto F">F Sallusto</name></author><author><name sortKey="Lanzavecchia, A" uniqKey="Lanzavecchia A">A Lanzavecchia</name></author><author><name sortKey="Araki, K" uniqKey="Araki K">K Araki</name></author><author><name sortKey="Ahmed, R" uniqKey="Ahmed R">R Ahmed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sandoval, H" uniqKey="Sandoval H">H Sandoval</name></author><author><name sortKey="Thiagarajan, P" uniqKey="Thiagarajan P">P Thiagarajan</name></author><author><name sortKey="Dasgupta, Sk" uniqKey="Dasgupta S">SK Dasgupta</name></author><author><name sortKey="Schumacher, A" uniqKey="Schumacher A">A Schumacher</name></author><author><name sortKey="Prchal, Jt" uniqKey="Prchal J">JT Prchal</name></author><author><name sortKey="Chen, M" uniqKey="Chen M">M Chen</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sato, N" uniqKey="Sato N">N Sato</name></author><author><name sortKey="Patel, Hj" uniqKey="Patel H">HJ Patel</name></author><author><name sortKey="Waldmann, Ta" uniqKey="Waldmann T">TA Waldmann</name></author><author><name sortKey="Tagaya, Y" uniqKey="Tagaya Y">Y Tagaya</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schweers, Rl" uniqKey="Schweers R">RL Schweers</name></author><author><name sortKey="Zhang, J" uniqKey="Zhang J">J Zhang</name></author><author><name sortKey="Randall, Ms" uniqKey="Randall M">MS Randall</name></author><author><name sortKey="Loyd, Mr" uniqKey="Loyd M">MR Loyd</name></author><author><name sortKey="Li, W" uniqKey="Li W">W Li</name></author><author><name sortKey="Dorsey, Fc" uniqKey="Dorsey F">FC Dorsey</name></author><author><name sortKey="Kundu, M" uniqKey="Kundu M">M Kundu</name></author><author><name sortKey="Opferman, Jt" uniqKey="Opferman J">JT Opferman</name></author><author><name sortKey="Cleveland, Jl" uniqKey="Cleveland J">JL Cleveland</name></author><author><name sortKey="Miller, Jl" uniqKey="Miller J">JL Miller</name></author><author><name sortKey="Ney, Pa" uniqKey="Ney P">PA Ney</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Secinaro, Ma" uniqKey="Secinaro M">MA Secinaro</name></author><author><name sortKey="Fortner, Ka" uniqKey="Fortner K">KA Fortner</name></author><author><name sortKey="Dienz, O" uniqKey="Dienz O">O Dienz</name></author><author><name sortKey="Logan, A" uniqKey="Logan A">A Logan</name></author><author><name sortKey="Murphy, Mp" uniqKey="Murphy M">MP Murphy</name></author><author><name sortKey="Anathy, V" uniqKey="Anathy V">V Anathy</name></author><author><name sortKey="Boyson, Je" uniqKey="Boyson J">JE Boyson</name></author><author><name sortKey="Budd, Rc" uniqKey="Budd R">RC Budd</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shefa, U" uniqKey="Shefa U">U Shefa</name></author><author><name sortKey="Jeong, Ny" uniqKey="Jeong N">NY Jeong</name></author><author><name sortKey="Song, Io" uniqKey="Song I">IO Song</name></author><author><name sortKey="Chung, H J" uniqKey="Chung H">H-J Chung</name></author><author><name sortKey="Kim, D" uniqKey="Kim D">D Kim</name></author><author><name sortKey="Jung, J" uniqKey="Jung J">J Jung</name></author><author><name sortKey="Huh, Y" uniqKey="Huh Y">Y Huh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shimomura, Y" uniqKey="Shimomura Y">Y Shimomura</name></author><author><name sortKey="Honda, T" uniqKey="Honda T">T Honda</name></author><author><name sortKey="Shiraki, M" uniqKey="Shiraki M">M Shiraki</name></author><author><name sortKey="Murakami, T" uniqKey="Murakami T">T Murakami</name></author><author><name sortKey="Sato, J" uniqKey="Sato J">J Sato</name></author><author><name sortKey="Kobayashi, H" uniqKey="Kobayashi H">H Kobayashi</name></author><author><name sortKey="Mawatari, K" uniqKey="Mawatari K">K Mawatari</name></author><author><name sortKey="Obayashi, M" uniqKey="Obayashi M">M Obayashi</name></author><author><name sortKey="Harris, Ra" uniqKey="Harris R">RA Harris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stemmer, M" uniqKey="Stemmer M">M Stemmer</name></author><author><name sortKey="Thumberger, T" uniqKey="Thumberger T">T Thumberger</name></author><author><name sortKey="Del Sol Keyer, M" uniqKey="Del Sol Keyer M">M Del Sol Keyer</name></author><author><name sortKey="Wittbrodt, J" uniqKey="Wittbrodt J">J Wittbrodt</name></author><author><name sortKey="Mateo, Jl" uniqKey="Mateo J">JL Mateo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sugiura, A" uniqKey="Sugiura A">A Sugiura</name></author><author><name sortKey="Rathmell, Jc" uniqKey="Rathmell J">JC Rathmell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tata, A" uniqKey="Tata A">A Tata</name></author><author><name sortKey="Brossay, L" uniqKey="Brossay L">L Brossay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Der Windt, Gjw" uniqKey="Van Der Windt G">GJW van der Windt</name></author><author><name sortKey="Everts, B" uniqKey="Everts B">B Everts</name></author><author><name sortKey="Chang, Ch" uniqKey="Chang C">CH Chang</name></author><author><name sortKey="Curtis, Jd" uniqKey="Curtis J">JD Curtis</name></author><author><name sortKey="Freitas, Tc" uniqKey="Freitas T">TC Freitas</name></author><author><name sortKey="Amiel, E" uniqKey="Amiel E">E Amiel</name></author><author><name sortKey="Pearce, Ej" uniqKey="Pearce E">EJ Pearce</name></author><author><name sortKey="Pearce, El" uniqKey="Pearce E">EL Pearce</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Der Windt, Gjw" uniqKey="Van Der Windt G">GJW van der Windt</name></author><author><name sortKey="O Ullivan, D" uniqKey="O Ullivan D">D O’Sullivan</name></author><author><name sortKey="Everts, B" uniqKey="Everts B">B Everts</name></author><author><name sortKey="Huang, Sc" uniqKey="Huang S">SC Huang</name></author><author><name sortKey="Buck, Md" uniqKey="Buck M">MD Buck</name></author><author><name sortKey="Curtis, Jd" uniqKey="Curtis J">JD Curtis</name></author><author><name sortKey="Chang, Ch" uniqKey="Chang C">CH Chang</name></author><author><name sortKey="Smith, Am" uniqKey="Smith A">AM Smith</name></author><author><name sortKey="Ai, T" uniqKey="Ai T">T Ai</name></author><author><name sortKey="Faubert, B" uniqKey="Faubert B">B Faubert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Duikeren, S" uniqKey="Van Duikeren S">S van Duikeren</name></author><author><name sortKey="Fransen, Mf" uniqKey="Fransen M">MF Fransen</name></author><author><name sortKey="Redeker, A" uniqKey="Redeker A">A Redeker</name></author><author><name sortKey="Wieles, B" uniqKey="Wieles B">B Wieles</name></author><author><name sortKey="Platenburg, G" uniqKey="Platenburg G">G Platenburg</name></author><author><name sortKey="Krebber, Wj" uniqKey="Krebber W">WJ Krebber</name></author><author><name sortKey="Ossendorp, F" uniqKey="Ossendorp F">F Ossendorp</name></author><author><name sortKey="Melief, Cj" uniqKey="Melief C">CJ Melief</name></author><author><name sortKey="Arens, R" uniqKey="Arens R">R Arens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vantaku, V" uniqKey="Vantaku V">V Vantaku</name></author><author><name sortKey="Donepudi, Sr" uniqKey="Donepudi S">SR Donepudi</name></author><author><name sortKey="Ambati, Cr" uniqKey="Ambati C">CR Ambati</name></author><author><name sortKey="Jin, F" uniqKey="Jin F">F Jin</name></author><author><name sortKey="Putluri, V" uniqKey="Putluri V">V Putluri</name></author><author><name sortKey="Nguyen, K" uniqKey="Nguyen K">K Nguyen</name></author><author><name sortKey="Rajapakshe, K" uniqKey="Rajapakshe K">K Rajapakshe</name></author><author><name sortKey="Coarfa, C" uniqKey="Coarfa C">C Coarfa</name></author><author><name sortKey="Battula, Vl" uniqKey="Battula V">VL Battula</name></author><author><name sortKey="Lotan, Y" uniqKey="Lotan Y">Y Lotan</name></author><author><name sortKey="Putluri, N" uniqKey="Putluri N">N Putluri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vockley, J" uniqKey="Vockley J">J Vockley</name></author><author><name sortKey="Mohsen Al W, A" uniqKey="Mohsen Al W A">A Mohsen al-W</name></author><author><name sortKey="Binzak, B" uniqKey="Binzak B">B Binzak</name></author><author><name sortKey="Willard, J" uniqKey="Willard J">J Willard</name></author><author><name sortKey="Fauq, A" uniqKey="Fauq A">A Fauq</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Voehringer, D" uniqKey="Voehringer D">D Voehringer</name></author><author><name sortKey="Koschella, M" uniqKey="Koschella M">M Koschella</name></author><author><name sortKey="Pircher, H" uniqKey="Pircher H">H Pircher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Walter, Dm" uniqKey="Walter D">DM Walter</name></author><author><name sortKey="Venancio, Os" uniqKey="Venancio O">OS Venancio</name></author><author><name sortKey="Buza, El" uniqKey="Buza E">EL Buza</name></author><author><name sortKey="Tobias, Jw" uniqKey="Tobias J">JW Tobias</name></author><author><name sortKey="Deshpande, C" uniqKey="Deshpande C">C Deshpande</name></author><author><name sortKey="Gudiel, Aa" uniqKey="Gudiel A">AA Gudiel</name></author><author><name sortKey="Kim Kiselak, C" uniqKey="Kim Kiselak C">C Kim-Kiselak</name></author><author><name sortKey="Cicchini, M" uniqKey="Cicchini M">M Cicchini</name></author><author><name sortKey="Yates, Tj" uniqKey="Yates T">TJ Yates</name></author><author><name sortKey="Feldser, Dm" uniqKey="Feldser D">DM Feldser</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Watkins, Pa" uniqKey="Watkins P">PA Watkins</name></author><author><name sortKey="Lu, J F" uniqKey="Lu J">J-F Lu</name></author><author><name sortKey="Steinberg, Sj" uniqKey="Steinberg S">SJ Steinberg</name></author><author><name sortKey="Gould, Sj" uniqKey="Gould S">SJ Gould</name></author><author><name sortKey="Smith, Kd" uniqKey="Smith K">KD Smith</name></author><author><name sortKey="Braiterman, Lt" uniqKey="Braiterman L">LT Braiterman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weant, Ae" uniqKey="Weant A">AE Weant</name></author><author><name sortKey="Michalek, Rd" uniqKey="Michalek R">RD Michalek</name></author><author><name sortKey="Khan, Iu" uniqKey="Khan I">IU Khan</name></author><author><name sortKey="Holbrook, Bc" uniqKey="Holbrook B">BC Holbrook</name></author><author><name sortKey="Willingham, Mc" uniqKey="Willingham M">MC Willingham</name></author><author><name sortKey="Grayson, Jm" uniqKey="Grayson J">JM Grayson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Witte, I" uniqKey="Witte I">I Witte</name></author><author><name sortKey="Horke, S" uniqKey="Horke S">S Horke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, X" uniqKey="Xu X">X Xu</name></author><author><name sortKey="Araki, K" uniqKey="Araki K">K Araki</name></author><author><name sortKey="Li, S" uniqKey="Li S">S Li</name></author><author><name sortKey="Han, Jh" uniqKey="Han J">JH Han</name></author><author><name sortKey="Ye, L" uniqKey="Ye L">L Ye</name></author><author><name sortKey="Tan, Wg" uniqKey="Tan W">WG Tan</name></author><author><name sortKey="Konieczny, Bt" uniqKey="Konieczny B">BT Konieczny</name></author><author><name sortKey="Bruinsma, Mw" uniqKey="Bruinsma M">MW Bruinsma</name></author><author><name sortKey="Martinez, J" uniqKey="Martinez J">J Martinez</name></author><author><name sortKey="Pearce, El" uniqKey="Pearce E">EL Pearce</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, A" uniqKey="Xu A">A Xu</name></author><author><name sortKey="Bhanumathy, Kk" uniqKey="Bhanumathy K">KK Bhanumathy</name></author><author><name sortKey="Wu, J" uniqKey="Wu J">J Wu</name></author><author><name sortKey="Ye, Z" uniqKey="Ye Z">Z Ye</name></author><author><name sortKey="Freywald, A" uniqKey="Freywald A">A Freywald</name></author><author><name sortKey="Leary, Sc" uniqKey="Leary S">SC Leary</name></author><author><name sortKey="Li, R" uniqKey="Li R">R Li</name></author><author><name sortKey="Xiang, J" uniqKey="Xiang J">J Xiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Youngblood, B" uniqKey="Youngblood B">B Youngblood</name></author><author><name sortKey="Hale, Js" uniqKey="Hale J">JS Hale</name></author><author><name sortKey="Kissick, Ht" uniqKey="Kissick H">HT Kissick</name></author><author><name sortKey="Ahn, E" uniqKey="Ahn E">E Ahn</name></author><author><name sortKey="Xu, X" uniqKey="Xu X">X Xu</name></author><author><name sortKey="Wieland, A" uniqKey="Wieland A">A Wieland</name></author><author><name sortKey="Araki, K" uniqKey="Araki K">K Araki</name></author><author><name sortKey="West, Ee" uniqKey="West E">EE West</name></author><author><name sortKey="Ghoneim, He" uniqKey="Ghoneim H">HE Ghoneim</name></author><author><name sortKey="Fan, Y" uniqKey="Fan Y">Y Fan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yu, D" uniqKey="Yu D">D Yu</name></author><author><name sortKey="Ye, L" uniqKey="Ye L">L Ye</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yuzefpolskiy, Y" uniqKey="Yuzefpolskiy Y">Y Yuzefpolskiy</name></author><author><name sortKey="Baumann, Fm" uniqKey="Baumann F">FM Baumann</name></author><author><name sortKey="Kalia, V" uniqKey="Kalia V">V Kalia</name></author><author><name sortKey="Sarkar, S" uniqKey="Sarkar S">S Sarkar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, X" uniqKey="Zhou X">X Zhou</name></author><author><name sortKey="Xue, Hh" uniqKey="Xue H">HH Xue</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101573691</journal-id><journal-id journal-id-type="pubmed-jr-id">39703</journal-id><journal-id journal-id-type="nlm-ta">Cell Rep</journal-id><journal-id journal-id-type="iso-abbrev">Cell Rep</journal-id><journal-title-group><journal-title>Cell reports</journal-title></journal-title-group><issn pub-type="epub">2211-1247</issn></journal-meta><article-meta><article-id pub-id-type="pmid">31722203</article-id><article-id pub-id-type="pmc">6886713</article-id><article-id pub-id-type="doi">10.1016/j.celrep.2019.10.032</article-id><article-id pub-id-type="manuscript">NIHMS1542962</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>NIX-Mediated Mitophagy Promotes Effector Memory Formation in Antigen-Specific CD8<sup>+</sup> T Cells</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Gupta</surname><given-names>Shubhranshu S.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Sharp</surname><given-names>Robert</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Hofferek</surname><given-names>Colby</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Kuai</surname><given-names>Le</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Dorn</surname><given-names>Gerald W.</given-names><suffix>II</suffix></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Jin</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Min</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A6">6</xref><xref rid="CR1" ref-type="corresp">*</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA</aff><aff id="A2"><label>2</label>Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX 77030, USA</aff><aff id="A3"><label>3</label>Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA</aff><aff id="A4"><label>4</label>Immunobiology and Transplant Science Center, Houston Methodist Research Institute, Houston, TX 77030, USA</aff><aff id="A5"><label>5</label>Department of Surgery, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA</aff><aff id="A6"><label>6</label>Lead Contact</aff><author-notes><corresp id="CR1"><label>*</label>Correspondence: <email>minc@bcm.edu</email></corresp><fn fn-type="con" id="FN1"><p id="P1">AUTHOR CONTRIBUTIONS</p><p id="P2">S.S.G., R.S., and C.H. performed experiments involving flow cytometry. L.K. performed the thymic T cell development study. S.S.G. analyzed data and performed the rest of the experiments. G.D. generated NIX<sup>f/f</sup> mice. S.S.G. planned studies, designed experiments, and wrote the manuscript. M.C. and J.W. supervised the study and edited the manuscript.</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>15</day><month>11</month><year>2019</year></pub-date><pub-date pub-type="ppub"><day>12</day><month>11</month><year>2019</year></pub-date><pub-date pub-type="pmc-release"><day>02</day><month>12</month><year>2019</year></pub-date><volume>29</volume><issue>7</issue><fpage>1862</fpage><lpage>1877.e7</lpage><pmc-comment>elocation-id from pubmed: 10.1016/j.celrep.2019.10.032</pmc-comment>
<permissions><license license-type="open-access"><license-p>This is an open access article under the CC BY-NC-ND license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0/">http://creativecommons.org/licenses/by-nc-nd/4.0/</ext-link>)</license-p></license></permissions><abstract id="ABS1"><title>SUMMARY</title><p id="P3">Autophagy plays a critical role in the maintenance of immunological memory. However, the molecular mechanisms involved in autophagy-regulated effector memory formation in CD8<sup>+</sup> T cells remain unclear. Here we show that deficiency in NIX-dependent mitophagy leads to metabolic defects in effector memory T cells. Deletion of NIX caused HIF1α accumulation and altered cellular metabolism from long-chain fatty acid to short/branched-chain fatty acid oxidation, thereby compromising ATP synthesis during effector memory formation. Preventing HIF1α accumulation restored long-chain fatty acid metabolism and effector memory formation in antigen-specific CD8<sup>+</sup> T cells. Our study suggests that NIX-mediated mitophagy is critical for effector memory formation in T cells.</p></abstract><abstract id="ABS2" abstract-type="graphical"><title>Graphical Abstract</title><p id="P4"><graphic xlink:href="nihms-1542962-f0001.jpg" position="anchor" orientation="portrait"></graphic></p></abstract><abstract id="ABS3" abstract-type="summary"><title>In Brief</title><p id="P5">Gupta et al. demonstrate that mitophagy mediated by NIX, a mitochondrial outer membrane protein, plays a critical role in CD8<sup>+</sup> T cell effector memory formation by regulating mitochondrial superoxide-dependent HIF1α protein accumulation and fatty acid metabolism. These findings elucidate the molecular mechanisms regulating T cell effector memory formation against viruses.</p></abstract></article-meta></front><floats-group><fig id="F1" orientation="portrait" position="float"><label>Figure 1.</label><caption><title>NIX Is Critical for Formation of Effector Memory in Ova-Specific CD8<sup>+</sup> T Cells</title><p id="P72">Spleens from OT-I mice (A–D) or wild-type (WT) and T/NIX<sup>−/−</sup> mice (E–K) were collected at designated time points.</p><p id="P73">(A) Kinetics of <italic>Nix</italic> expression in Ova-specific CD8<sup>+</sup> T cells (Ova-CD8<sup>+</sup>) after VSV-Ova immunization.</p><p id="P74">(B) Gene expression of <italic>Nix</italic> in Ova-CD8<sup>+</sup> 24 h after addition of IL-15. CD8<sup>+</sup> T cells from naive OT-I mice were activated with anti-CD3 and anti-CD28 for 72 h, followed by IL-15 addition.</p><p id="P75">(C) Kinetics of <italic>Nix</italic> expression in Ova-CD8<sup>+</sup> after CD3-stimulation, followed by IL-15 addition.</p><p id="P76">(D) Kinetics of <italic>Il15ra</italic> expression in Ova-CD8<sup>+</sup> after VSV-Ova immunization. Ova-CD8<sup>+</sup> from mice within the same experimental group in (A)–(D) were pooled before analysis.</p><p id="P77">(E) Representative dot plot showing percentage of Ova-EM in WT or T/NIX<sup>−/−</sup> spleens on day 30 p.i. with 10<sup>4</sup> plaque-forming units (PFU) of VSV-Ova.</p><p id="P78">(F) Mean frequencies of Ova-EM from (E).</p><p id="P79">(G) Experimental model for adoptive transfer experiment performed in (H).</p><p id="P80">(H) Left: representative plot showing percentages of CD45.1<sup>+</sup> WT and CD45.2<sup>+</sup> T/NIX<sup>−/−</sup> Ova-EM in CD45.2<sup>+</sup> T/NIX<sup>−/−</sup> mice 30 days after VSV-Ova immunization. Right: mean frequencies of CD45.1<sup>+</sup> WT and CD45.2<sup>+</sup> T/NIX<sup>−/−</sup> Ova-EM from experiment performed in the left panel.</p><p id="P81">(I) Kinetics of effector memory formation in Ova-CD8<sup>+</sup><italic>in vivo</italic> in WT or T/NIX<sup>−/−</sup> mice after VSV-Ova immunization.</p><p id="P82">(J) Gene expression of <italic>Nix</italic> in day 0 naive, day 6 Ova-activated, day 10 Ova-CD8<sup>+</sup> MPECs, day 30 Ova-EM, and day 30 Ova-CM in WT mice after VSV-Ova immunization.</p><p id="P83">(K and L) Gene expression of <italic>Foxo1</italic> (left panel) and <italic>Tcf7</italic> (right panel) in day 10 Ova-CD8<sup>+</sup> MPECs (K) or day 30 Ova-EM (L) harvested from WT or T/NIX<sup>−/−</sup> spleens after VSV-Ova immunization.</p><p id="P84">(M) <italic>In vitro</italic> differentiation of Ova-EM. Left: representative plot for percentage of WT or T/NIX<sup>−/−</sup> Ova-EM on day 8. Right: mean frequency of Ova-EM from left panel.</p><p id="P85">In (E) and (M), CD8<sup>+</sup>Ova_tetramer<sup>+</sup> population (Ova-EM) was gated on CD3<sup>+</sup>CD8<sup>+</sup>CD43<sup>−</sup>CD62L<sup>−</sup>CD44<sup>+</sup> population. Data are representative of two or more independent experiments (n = 3–10). Data were analyzed using one-way ANOVA with Bonferroni’s posttest (mean ± SEM) in (A)–(D); two-tailed Student’s t test (mean ± SEM) in (F), (H, right), (J)–(L), and (M, right); and two-way ANOVA with Bonferroni’s posttests (mean ± SEM) in (I). *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001. See also <xref rid="SD1" ref-type="supplementary-material">Figures S1</xref> and <xref rid="SD1" ref-type="supplementary-material">S2</xref>.</p></caption><graphic xlink:href="nihms-1542962-f0002"></graphic></fig><fig id="F2" orientation="portrait" position="float"><label>Figure 2.</label><caption><title>Deletion of NIX Leads to an Impaired Memory Recall in Ova-Specific Effector Memory CD8<sup>+</sup> T Cells</title><p id="P86">Ova-EM formed <italic>in vivo</italic> (A–E) or <italic>in vitro</italic> (F–I) from CD45.2<sup>+</sup> WT or T/NIX<sup>−/−</sup> mice were adoptively transferred into naive CD45.1<sup>+</sup> mice. CD45.1<sup>+</sup> hosts were challenged with 10<sup>4</sup> PFU of VSV-Ova 24 h later. Forty-eight hours later, spleen and serum were harvested for analyses.</p><p id="P87">(A) CD45.2<sup>+</sup> Ova-CD8<sup>+</sup> in CD45.1<sup>+</sup> recipients receiving <italic>in vivo</italic> generated CD45.2<sup>+</sup> WT or T/NIX<sup>−/−</sup> Ova-EM.</p><p id="P88">(B) Serum IFN-γ (left) and IL-2 (right) in CD45.1<sup>+</sup> recipients from (A).</p><p id="P89">(C) Plot showing IFN-γ and IL-2 producing CD45.2<sup>+</sup> Ova-CD8<sup>+</sup> in CD45.1<sup>+</sup> recipients receiving <italic>in vivo</italic> generated CD45.2<sup>+</sup> WT or T/NIX<sup>−/−</sup> Ova-EM.</p><p id="P90">(D) Intracellular IFN-γ and IL-2 in CD45.2<sup>+</sup> Ova-CD8<sup>+</sup> in CD45.1<sup>+</sup> recipients receiving CD45.2<sup>+</sup> WT or T/NIX<sup>−/−</sup> Ova-EM. Geometric mean fluorescence index (MFI) values for IFN-γ were 2,292 ± 130.1 (WT) and 1,831 ± 143.6 (T/NIX<sup>−/−</sup>). Geometric MFIs for IL-2 were 1,126 ± 88.91 (WT) and 920.7 ± 166.3 (T/NIX<sup>−/−</sup>).</p><p id="P91">(E) <italic>In vivo</italic> proliferation of re-activated WT or T/NIX<sup>−/−</sup> Ova-EM measured by CFSE staining. Peaks corresponding to G1, G2, G3, G4, and G5 represent the generations of cells after successive cell division cycles. Proliferation index: 1.611 ± 0.023 (WT) and 1.454 ± 0.026 (T/NIX<sup>−/−</sup>) (p < 0.001).</p><p id="P92">(F) CD45.2<sup>+</sup> Ova-CD8<sup>+</sup> in CD45.1<sup>+</sup> recipients receiving <italic>in vitro</italic> generated CD45.2<sup>+</sup> WT or T/NIX<sup>−/−</sup> Ova-EM.</p><p id="P93">(G) Serum IFN-γ and IL-2 in CD45.1<sup>+</sup> recipients from (F).</p><p id="P94">(H) Plot showing frequencies of IFN-γ- and IL-2-producing CD45.2<sup>+</sup> Ova-CD8<sup>+</sup> in CD45.1<sup>+</sup> recipients receiving <italic>in vitro</italic> generated CD45.2<sup>+</sup> WT or T/NIX<sup>−/−</sup> Ova-EM.</p><p id="P95">(I) Intracellular IFN-γ and IL-2 in CD45.2<sup>+</sup> Ova-CD8<sup>+</sup> in CD45.1<sup>+</sup> recipients receiving <italic>in vitro</italic> generated CD45.2<sup>+</sup> WT or T/NIX<sup>−/−</sup> Ova-EM. Geometric MFIs for IFN-γ were 7,120 ± 503.1 (WT) and 5,363 ± 551.3 (T/NIX<sup>−/−</sup>). Geometric MFIs for IL-2 were 5,154 ± 394.6 (WT) and 2,668 ± 489.4 (T/NIX<sup>−/−</sup>).</p><p id="P96">Data in (A), (B), and (E)–(G) are representative of two or more independent experiments (n = 3–9), and data in (C), (D), (H), and (I) are representative of three or four biological replicates per group. Data were analyzed using two-tailed Student’s t test (mean ± SEM). *p < 0.05, **p < 0.01, and ***p < 0.001. See also <xref rid="SD1" ref-type="supplementary-material">Figure S3</xref>.</p></caption><graphic xlink:href="nihms-1542962-f0003"></graphic></fig><fig id="F3" orientation="portrait" position="float"><label>Figure 3.</label><caption><title>Deletion of NIX Leads to Mitochondrial Accumulation in Ova-Specific Effector Memory CD8<sup>+</sup> T Cells</title><p id="P97">Spleens from WT or T/NIX<sup>−/−</sup> mice were collected 30 days p.i. with VSV-Ova for analyses.</p><p id="P98">(A) Top: MitoTracker Green staining in Ova-EM. Bottom: geometric mean fluorescence index (MFI) of MitoTracker Green staining from top panel.</p><p id="P99">(B) Representative image of WT or T/NIX<sup>−/−</sup> Ova-EM stained with COX IV (mitochondria) and LC3 (autophagosomes) obtained by immunocytochemistry.</p><p id="P100">(C and D) Mitochondrial median fluorescence index (MFI) (C) and (D) co-localization analysis of mitochondria and autophagosomes in Ova-EM from (B). For each independent experiment in (B)–(D), Ova-EM were pooled from mice within the same experimental group, and 150 cells/group were imaged. Each point represents one Ova-EM.</p><p id="P101">(E) Gene expression of <italic>Tfam</italic> in Ova-EM. Ova-EM from mice within the same experimental group were pooled before analysis.</p><p id="P102">(F) Intracellular staining of TFAM in Ova-EM.</p><p id="P103">Data are representative of two or more independent experiments (n = 5–7). Data were analyzed using two-tailed Student’s t test (mean ± SEM). **p < 0.01, ***p < 0.001, and ****p < 0.0001. ns, non-significant. See also <xref rid="SD1" ref-type="supplementary-material">Figure S4</xref>.</p></caption><graphic xlink:href="nihms-1542962-f0004"></graphic></fig><fig id="F4" orientation="portrait" position="float"><label>Figure 4.</label><caption><title>Deletion of NIX Results in Elevation of Mitochondrial Superoxide, Thereby Impairing CD8<sup>+</sup> T Cell Effector Memory Formation during Contraction Phase</title><p id="P104">Spleens from WT and T/NIX<sup>−/−</sup> mice were harvested on designated time points after immunization with 10<sup>4</sup> PFU VSV-Ova.</p><p id="P105">(A) MitoSOX Red staining in Ova-CD8<sup>+</sup> from WT and T/NIX<sup>−/−</sup> mice 20 days p.i.</p><p id="P106">(B) Geometric MFI for mitochondrial superoxide in Ova-CD8<sup>+</sup> from (A).</p><p id="P107">(C) Mitochondrial membrane depolarization (JC-1 monomer fluorescence) in Ova-CD8<sup>+</sup> from WT and T/NIX<sup>−/−</sup> mice 20 days p.i.</p><p id="P108">(D) Geometric MFI for JC-1 fluorescence in Ova-CD8<sup>+</sup> from (C).</p><p id="P109">(E) Representative plot showing percentage of Ova-EM 30 days p.i. in WT and T/NIX<sup>−/−</sup> mice that were treated with NAC or vehicle control (PBS) on days 13, 20, and 27 p.i.</p><p id="P110">(F) Mean frequencies of Ova-EM from (E).</p><p id="P111">(G) Representative plot showing percentage of WT and T/NIX<sup>−/−</sup> Ova-EM formed <italic>in vitro</italic>, after NAC or PBS treatment.</p><p id="P112">(H) Mean frequencies of Ova-EM from (G).</p><p id="P113">Data are representative of two or more independent experiments (n = 6–10). Data were analyzed using two-tailed Student’s t test (mean ± SEM). *p < 0.05, **p < 0.01, and ****p < 0.0001. ns, non-significant. See also <xref rid="SD1" ref-type="supplementary-material">Figure S5</xref>.</p></caption><graphic xlink:href="nihms-1542962-f0005"></graphic></fig><fig id="F5" orientation="portrait" position="float"><label>Figure 5.</label><caption><title>Mitochondrial Superoxide Elevates HIF1α during Contraction Phase in T/NIX<sup>−/−</sup> Mice</title><p id="P114">Spleens from WT or T/NIX<sup>−/−</sup> mice were collected at designated time points after immunization with 10<sup>4</sup> PFU VSV-Ova.</p><p id="P115">(A) Intracellular HIF1α protein level in Ova-EM 30 days p.i. in WT and T/NIX<sup>−/−</sup> mice.</p><p id="P116">(B) Geometric MFI of HIF1α protein staining from (A).</p><p id="P117">(C) Intracellular HIF1α protein level in Ova-specific effector CD8<sup>+</sup> T cells during peak primary response (day 6 p.i.) and contraction phase (day 13 p.i.) in WT and T/NIX<sup>−/−</sup> mice.</p><p id="P118">(D) Geometric MFI of HIF1α protein staining from (C).</p><p id="P119">(E) Intracellular HIF1α protein level in Ova-CD8<sup>+</sup> in NAC or PBS treated WT and T/NIX<sup>−/−</sup> mice.</p><p id="P120">(F) Geometric MFI of HIF1α protein staining from (E).</p><p id="P121">Data are representative of two or more independent experiments (n = 3–12). Data were analyzed using two-tailed Student’s t test (mean ± SEM) in (B) and (F) and two-way ANOVA with Bonferroni’s posttest (mean ± SEM) in (D). **p < 0.01, ***p < 0.001, and ****p < 0.0001. ns, non-significant. See also <xref rid="SD1" ref-type="supplementary-material">Figure S5</xref>.</p></caption><graphic xlink:href="nihms-1542962-f0006"></graphic></fig><fig id="F6" orientation="portrait" position="float"><label>Figure 6.</label><caption><title>Elevated HIF1α Alters Mitochondrial Fatty Acid Metabolism during CD8<sup>+</sup> T Cell Effector Memory Formation in T/NIX<sup>−/−</sup> Mice, Leading to Impairment in ATP Synthesis</title><p id="P122">(A) Gene expression of <italic>Fasn</italic> in Ova-EM 30 days after immunization with 10<sup>4</sup> VSV-Ova.</p><p id="P123">(B and C) Gene expression of T cell metabolic genes (B) and <italic>Bckdk</italic> (C) in Ova-EM 30 days after VSV-Ova immunization in WT and T/NIX<sup>−/−</sup> mice.</p><p id="P124">(D) Gene expression of <italic>Fasn</italic> (left panel) and <italic>Bckdk</italic> (right panel) in Ova-EM formed <italic>in vitro</italic> (vehicle or CAY10585 treatment on day 4).</p><p id="P125">(E) Left: representative OCR in Ova-EM <italic>in vitro</italic> (vehicle or CAY10585 treated OT-I WT and OT-I T/NIX<sup>−/−</sup> cells). Right: fold change in long-chain fatty acid oxidation-linked OCR from left panel.</p><p id="P126">(F) Fold change in short/branched-chain fatty acid oxidation linked OCR in Ova-EM formed <italic>in vitro</italic> (vehicle or CAY10585 treated OT-I WT and OT-I T/NIX<sup>−/−</sup> cells).</p><p id="P127">(G) Effect of loss of ACADSB on effector memory formation in OT-I WT and OT-I T/NIX<sup>−/−</sup> cells transduced with LentiCRISPRv2 expressing sgRNA-control or sgRNA-ACADSB.</p><p id="P128">(H) Intracellular ATP level in Ova-EM 30 days p.i. in WT and T/NIX<sup>−/−</sup> mice.</p><p id="P129">(I) Intracellular ATP in Ova-EM formed <italic>in vitro</italic> (vehicle or CAY10585 treated WT or T/NIX<sup>−/−</sup> cells).</p><p id="P130">(J) Intracellular ATP in Ova-EM formed <italic>in vitro</italic> (sgRNA-control or sgRNA-HIF1α transduced OT-I WT or OT-I T/NIX<sup>−/−</sup> cells).</p><p id="P131">Ova-EM from all mice within the same experimental group in (A)–(F) and (H)–(J) were pooled for analysis. Each point represents an individual independent experiment. Data are representative of two or more independent experiments (n = 4–9). Data were analyzed using two-tailed Student’s t test (mean ± SEM). *p < 0.05, **p < 0.01, and ***p < 0.001. ns, non-significant. See also <xref rid="SD1" ref-type="supplementary-material">Figures S6</xref> and <xref rid="SD1" ref-type="supplementary-material">S7</xref>.</p></caption><graphic xlink:href="nihms-1542962-f0007"></graphic></fig><fig id="F7" orientation="portrait" position="float"><label>Figure 7.</label><caption><title>Inhibiting HIF1α Accumulation Restores Effector Memory Formation in Antigen-Specific T/NIX<sup>−/−</sup> CD8<sup>+</sup> T cells</title><p id="P132">(A) Representative plot showing percentage of Ova-EM formed <italic>in vitro</italic> from WT and T/NIX<sup>−/−</sup> splenocytes (treated with vehicle or CAY10585 on day 4).</p><p id="P133">(B) Mean frequency of Ova-EM from (A).</p><p id="P134">(C) Effect of loss of HIF1α on effector memory formation. OT-I WT or OT-I T/NIX<sup>−/−</sup> cells were transduced with LentiCRISPRv2 expressing sgRNA-HIF1α or sgRNA-control. Ova-EM from all mice within the same experimental group were combined. Each point represents an individual independent experiment.</p><p id="P135">(D) Mean frequency of Ova-EM formed <italic>in vitro</italic> from WT and T/NIX<sup>−/−</sup> splenocytes (treated with CAY10585 or CAY10585 and oligomycin).</p><p id="P136">(E and F) IFN-Υ concentration in the spleen (E) and (F) viral titer in the brains of mice 48 h after infection with 10<sup>6</sup> PFU of VSV-Ova. Naive C57/BL6J mice were injected with vehicle or CAY10585-treated WT or T/NIX<sup>−/−</sup> cells, generated as in (A), followed by infection with VSV-Ova.</p><p id="P137">Data in (A)–(D) are representative of two or more independent experiments (n = 5–8), and data in (E) and (F) are representative of four or five biological replicates per group. Data were analyzed by two-tailed Student’s t test (mean ± SEM). *p < 0.05, **p < 0.01, and ***p < 0.001. ns, non-significant. See also <xref rid="SD1" ref-type="supplementary-material">Figure S7</xref>.</p></caption><graphic xlink:href="nihms-1542962-f0008"></graphic></fig><table-wrap id="T1" position="float" orientation="portrait"><caption><p id="P138">KEY RESOURCES TABLE</p></caption><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col></colgroup><thead><tr><th align="left" valign="bottom" rowspan="1" colspan="1">REAGENT or RESOURCE</th><th align="left" valign="bottom" rowspan="1" colspan="1">SOURCE</th><th align="left" valign="bottom" rowspan="1" colspan="1">IDENTIFIER</th></tr></thead><tbody><tr><td colspan="3" align="left" valign="top" style="border-bottom: solid 1px" rowspan="1">Antibodies</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">APC anti-mouse CD3 antibody</td><td align="left" valign="top" rowspan="1" colspan="1">Biolegend</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_2561456; Cat#100236</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">APC anti-mouse CD8a antibody</td><td align="left" valign="top" rowspan="1" colspan="1">Biolegend</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_312751; Cat#100712</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Pacific Blue anti-mouse CD8a antibody</td><td align="left" valign="top" rowspan="1" colspan="1">Biolegend</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_493425; Cat#100725</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">APC/Fire 750 anti-mouse CD8a antibody</td><td align="left" valign="top" rowspan="1" colspan="1">Biolegend</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_2572113; Cat#100766</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">FITC anti-mouse/human CD44 antibody</td><td align="left" valign="top" rowspan="1" colspan="1">Biolegend</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_312957; Cat#103006</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">APC anti-mouse/human CD44 antibody</td><td align="left" valign="top" rowspan="1" colspan="1">Biolegend</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_312963; Cat#103012</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">APC/Fire 750 anti-mouse/human CD44 antibody</td><td align="left" valign="top" rowspan="1" colspan="1">Biolegend</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_2616727; Cat#103062</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">PE/Cy7 anti-mouse CD62L antibody</td><td align="left" valign="top" rowspan="1" colspan="1">Biolegend</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_313103; Cat#104418</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">APC/Fire 750 anti-mouse CD62L antibody</td><td align="left" valign="top" rowspan="1" colspan="1">Biolegend</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_2629772; Cat#104450</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">PerCP/Cy5.5 anti-mouse CD43 Activation-Associated Glycoform antibody</td><td align="left" valign="top" rowspan="1" colspan="1">Biolegend</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_2286556; Cat#121224</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">PE anti-mouse CD127 (IL-7Rα) Antibody</td><td align="left" valign="top" rowspan="1" colspan="1">Biolegend</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_1937251; Cat#135010</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Anti-mouse CD127 PE-Cy5 50 ug antibody</td><td align="left" valign="top" rowspan="1" colspan="1">Thermo Fisher Scientific</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_468792; Cat#15-1271-81</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">FITC Mouse Anti-Mouse CD45.2</td><td align="left" valign="top" rowspan="1" colspan="1">BD PharMingen</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_395041; Cat#553772</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">PE/Cy7 anti-mouse CD366 (Tim-3) Antibody</td><td align="left" valign="top" rowspan="1" colspan="1">Biolegend</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_2632733; Cat#134009</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Mouse TCF7/TCF1 Alexa Fluor® 647-conjugated Antibody</td><td align="left" valign="top" rowspan="1" colspan="1">R&D Systems</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#FAB8224R</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">PE/Cy7 anti-mouse/human KLRG1 (MAFA) antibody</td><td align="left" valign="top" rowspan="1" colspan="1">Biolegend</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_2561736; Cat#138416</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Brilliant Violet 605 anti-mouse CD185 (CXCR5) Antibody</td><td align="left" valign="top" rowspan="1" colspan="1">Biolegend</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_2562208; Cat#145513</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">PE/APC anti-mouse H-2K(b) SIINFEKL antibody (Ova_tetramer)</td><td align="left" valign="top" rowspan="1" colspan="1">Baylor College of Medicine MHC Tetramer Production Core</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#16114</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">FITC Annexin V</td><td align="left" valign="top" rowspan="1" colspan="1">BD PharMingen</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#51-65874X</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">CD3e antibody</td><td align="left" valign="top" rowspan="1" colspan="1">BD Biosciences</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_394591; Cat#553058</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Ultra-LEAF Purified anti-mouse CD3 antibody</td><td align="left" valign="top" rowspan="1" colspan="1">Biolegend</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_2616673; Cat#100359</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">CD28 antibody</td><td align="left" valign="top" rowspan="1" colspan="1">BD Biosciences</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_394763; Cat#553294</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Anti-mouse HIF-1 alpha Antibody</td><td align="left" valign="top" rowspan="1" colspan="1">Novus Biologicals</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_10001045; Cat#NB100-449</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Anti-mouse TFAM antibody</td><td align="left" valign="top" rowspan="1" colspan="1">Santa Cruz Biotechnology</td><td align="left" valign="top" rowspan="1" colspan="1">RRID: AB_10610743; Cat#sc-166965</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Anti-mouse ACADSB antibody</td><td align="left" valign="top" rowspan="1" colspan="1">Novus Biologicals</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#NBP1-97833</td></tr><tr><td colspan="3" align="left" valign="top" style="border-bottom: solid 1px; border-top: solid 1px" rowspan="1">Chemicals, Peptides, and Recombinant Proteins</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">CAY10585</td><td align="left" valign="top" rowspan="1" colspan="1">Cayman Chemical</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#<italic>934593-90-5</italic></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Ovalbumin</td><td align="left" valign="top" rowspan="1" colspan="1">Sigma-Aldrich</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#A7641</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">N-Acetyl-L-Cysteine (NAC)</td><td align="left" valign="top" rowspan="1" colspan="1">Sigma-Aldrich</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#A7250</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Hexadimethrine Bromide (polybrene)</td><td align="left" valign="top" rowspan="1" colspan="1">Sigma-Aldrich</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#H9268</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Etomoxir</td><td align="left" valign="top" rowspan="1" colspan="1">Sigma-Aldrich</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#E1905</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">FCCP</td><td align="left" valign="top" rowspan="1" colspan="1">Sigma-Aldrich</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#C2920</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Mouse IL-15</td><td align="left" valign="top" rowspan="1" colspan="1">Biolegend</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#566304</td></tr><tr><td colspan="3" align="left" valign="top" style="border-bottom: solid 1px; border-top: solid 1px" rowspan="1">Critical Commercial Assays</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">ATP Determination kit</td><td align="left" valign="top" rowspan="1" colspan="1">Molecular Probes</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#A22066</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Mouse IL-2 ELISA MAX Standard</td><td align="left" valign="top" rowspan="1" colspan="1">Biolegend</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#431002</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Mouse IFNg ELISA MAX Standard</td><td align="left" valign="top" rowspan="1" colspan="1">Biolegend</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#430802</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Mouse TNF ELISA Set</td><td align="left" valign="top" rowspan="1" colspan="1">BD Biosciences</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#555268</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">MitoSOX Red mitochondrial superoxide indicator</td><td align="left" valign="top" rowspan="1" colspan="1">Invitrogen</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#M36008</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Mitotracker Green FM</td><td align="left" valign="top" rowspan="1" colspan="1">Invitrogen</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#M7514</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">JC-1 dye</td><td align="left" valign="top" rowspan="1" colspan="1">Invitrogen</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#T3168</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Seahorse Xfe96 Flux assay kit</td><td align="left" valign="top" rowspan="1" colspan="1">Agilent Technologies</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#101085-004</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Mouse DNA Damage Analysis Kit</td><td align="left" valign="top" rowspan="1" colspan="1">Detroit R&D</td><td align="left" valign="top" rowspan="1" colspan="1">Cat#DD2M</td></tr><tr><td colspan="3" align="left" valign="top" style="border-bottom: solid 1px; border-top: solid 1px" rowspan="1">Experimental Models: Cell Lines</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">NIH 3T3</td><td align="left" valign="top" rowspan="1" colspan="1">CLS</td><td align="left" valign="top" rowspan="1" colspan="1">CVCL_0594</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">293T</td><td align="left" valign="top" rowspan="1" colspan="1">ATCC</td><td align="left" valign="top" rowspan="1" colspan="1">CVCL_0063</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">BHK-21</td><td align="left" valign="top" rowspan="1" colspan="1">CLS</td><td align="left" valign="top" rowspan="1" colspan="1">CVCL_1915</td></tr><tr><td colspan="3" align="left" valign="top" style="border-bottom: solid 1px; border-top: solid 1px" rowspan="1">Experimental Models: Organisms/Strains</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Mouse: C57BL/6J</td><td align="left" valign="top" rowspan="1" colspan="1">The Jackson Laboratory</td><td align="left" valign="top" rowspan="1" colspan="1">IMSR_JAX:000664</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Mouse: NIX<sup>f/f</sup></td><td align="left" valign="top" rowspan="1" colspan="1"><xref rid="R30" ref-type="bibr">Diwan et al., 2007</xref></td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Mouse: B6.Cg-Tg(Lck-cre)548Jxm/J</td><td align="left" valign="top" rowspan="1" colspan="1">The Jackson Laboratory</td><td align="left" valign="top" rowspan="1" colspan="1">IMSR_JAX:003802</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Mouse: C57BL/6-Tg(TcraTcrb)1100Mjb/J</td><td align="left" valign="top" rowspan="1" colspan="1">The Jackson Laboratory</td><td align="left" valign="top" rowspan="1" colspan="1">IMSR_JAX:003831</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Mouse: B6.SJL-Ptprc<sup>a</sup> Pep3<sup>b</sup>/BoyJ, Pep Boy, B6 Cd45.1</td><td align="left" valign="top" rowspan="1" colspan="1">The Jackson Laboratory</td><td align="left" valign="top" rowspan="1" colspan="1">IMSR_JAX:002014</td></tr><tr><td colspan="3" align="left" valign="top" style="border-bottom: solid 1px; border-top: solid 1px" rowspan="1">Oligonucleotides</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>18S</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Nix</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Bnip3</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Il-15rα</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Foxo1</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Tcf7</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Blimp-1</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Tfam</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Fasn</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Bckdk</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Acadl</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Acadsb</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Acadm</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Acads</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Acad11</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Atp5b</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Atp5f1</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Ehhadh</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Gls</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Glut1</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Prkaa1</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Pdha1</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Pink1</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Parkin</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1"><xref rid="R13" ref-type="bibr">Bian et al., 2012</xref></td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Caspase-3</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Hif1α</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Hif1α<sup>2nd</sup></italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primers for <italic>Acadsb</italic>, see <xref rid="SD1" ref-type="supplementary-material">Table S1</xref></td><td align="left" valign="top" rowspan="1" colspan="1">This paper</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td colspan="3" align="left" valign="top" style="border-bottom: solid 1px; border-top: solid 1px" rowspan="1">Software and Algorithms</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">FlowJo</td><td align="left" valign="top" rowspan="1" colspan="1">FlowJo, LLC</td><td align="left" valign="top" rowspan="1" colspan="1">SCR_008520</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Prism</td><td align="left" valign="top" rowspan="1" colspan="1">GraphPad Software</td><td align="left" valign="top" rowspan="1" colspan="1">SCR_002798</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">SoftWorx</td><td align="left" valign="top" rowspan="1" colspan="1">Applied Precision</td><td align="left" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Seahorse Wave</td><td align="left" valign="top" rowspan="1" colspan="1">Agilent Technologies</td><td align="left" valign="top" rowspan="1" colspan="1">SCR_014526</td></tr><tr><td colspan="3" align="left" valign="top" style="border-bottom: solid 1px; border-top: solid 1px" rowspan="1">Recombinant DNA</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">psPAX</td><td align="left" valign="top" rowspan="1" colspan="1">Didier Trono Lab</td><td align="left" valign="top" rowspan="1" colspan="1">Addgene_12260</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">pMD2.G</td><td align="left" valign="top" rowspan="1" colspan="1">Didier Trono Lab</td><td align="left" valign="top" rowspan="1" colspan="1">Addgene_12259</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">LentiCRISPRv2 plasmid</td><td align="left" valign="top" rowspan="1" colspan="1"><xref rid="R107" ref-type="bibr">Walter et al., 2017</xref></td><td align="left" valign="top" rowspan="1" colspan="1">Addgene_82416</td></tr></tbody></table></table-wrap><boxed-text id="BX1" position="float" orientation="portrait"><caption><title>Highlights</title></caption><list list-type="bullet" id="L2"><list-item><p id="P139">NIX regulates mitophagy during effector memory formation in CD8<sup>+</sup> T cells</p></list-item><list-item><p id="P140">NIX-mediated mitophagy prevents HIF1α accumulation during contraction phase</p></list-item><list-item><p id="P141">HIF1α alters metabolism from long-chain to short/branched-chain fatty acid oxidation</p></list-item><list-item><p id="P142">Optimal ATP generation is critical for effector memory formation in CD8<sup>+</sup> T cells</p></list-item></list></boxed-text></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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