mTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation.
Identifieur interne : 000687 ( Main/Exploration ); précédent : 000686; suivant : 000688mTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation.
Auteurs : Charles Sinclair [États-Unis] ; Gayathri Bommakanti [États-Unis] ; Luiz Gardinassi [États-Unis] ; Jens Loebbermann [États-Unis] ; Matthew Joseph Johnson [États-Unis] ; Paul Hakimpour [États-Unis] ; Thomas Hagan [États-Unis] ; Lydia Benitez [États-Unis] ; Andrei Todor [États-Unis] ; Deepa Machiah [États-Unis] ; Timothy Oriss [États-Unis] ; Anuradha Ray [États-Unis] ; Steven Bosinger [États-Unis] ; Rajesh Ravindran [États-Unis] ; Shuzhao Li [États-Unis] ; Bali Pulendran [États-Unis]Source :
- Science (New York, N.Y.) [ 1095-9203 ] ; 2017.
Descripteurs français
- KwdFr :
- Acides gras (métabolisme), Animaux (MeSH), Antigènes CD (métabolisme), Antigènes CD11b (génétique), Antigènes CD11b (métabolisme), Cellules Th17 (immunologie), Cellules dendritiques (immunologie), Granulocytes neutrophiles (immunologie), Granulocytes éosinophiles (immunologie), Homéostasie (MeSH), Hypersensibilité (métabolisme), Inflammation (métabolisme), Interleukine-23 (métabolisme), Intégrines alpha (métabolisme), Lymphocytes auxiliaires Th2 (immunologie), Oxydoréduction (MeSH), Poumon (anatomopathologie), Poumon (métabolisme), Présentation d'antigène (MeSH), Souris (MeSH), Souris de lignée C57BL (MeSH), Sérine-thréonine kinases TOR (génétique), Sérine-thréonine kinases TOR (métabolisme).
- MESH :
- anatomopathologie : Poumon.
- génétique : Antigènes CD11b, Sérine-thréonine kinases TOR.
- immunologie : Cellules Th17, Cellules dendritiques, Granulocytes neutrophiles, Granulocytes éosinophiles, Lymphocytes auxiliaires Th2.
- métabolisme : Acides gras, Antigènes CD, Antigènes CD11b, Hypersensibilité, Inflammation, Interleukine-23, Intégrines alpha, Poumon, Sérine-thréonine kinases TOR.
- Animaux, Homéostasie, Oxydoréduction, Présentation d'antigène, Souris, Souris de lignée C57BL.
English descriptors
- KwdEn :
- Animals (MeSH), Antigen Presentation (MeSH), Antigens, CD (metabolism), CD11b Antigen (genetics), CD11b Antigen (metabolism), Dendritic Cells (immunology), Eosinophils (immunology), Fatty Acids (metabolism), Homeostasis (MeSH), Hypersensitivity (metabolism), Inflammation (metabolism), Integrin alpha Chains (metabolism), Interleukin-23 (metabolism), Lung (metabolism), Lung (pathology), Mice (MeSH), Mice, Inbred C57BL (MeSH), Neutrophils (immunology), Oxidation-Reduction (MeSH), TOR Serine-Threonine Kinases (genetics), TOR Serine-Threonine Kinases (metabolism), Th17 Cells (immunology), Th2 Cells (immunology).
- MESH :
- chemical , genetics : CD11b Antigen, TOR Serine-Threonine Kinases.
- chemical , metabolism : Antigens, CD, CD11b Antigen, Fatty Acids, Integrin alpha Chains, Interleukin-23, TOR Serine-Threonine Kinases.
- immunology : Dendritic Cells, Eosinophils, Neutrophils, Th17 Cells, Th2 Cells.
- metabolism : Hypersensitivity, Inflammation, Lung.
- pathology : Lung.
- Animals, Antigen Presentation, Homeostasis, Mice, Mice, Inbred C57BL, Oxidation-Reduction.
Abstract
Antigen-presenting cells (APCs) occupy diverse anatomical tissues, but their tissue-restricted homeostasis remains poorly understood. Here, working with mouse models of inflammation, we found that mechanistic target of rapamycin (mTOR)-dependent metabolic adaptation was required at discrete locations. mTOR was dispensable for dendritic cell (DC) homeostasis in secondary lymphoid tissues but necessary to regulate cellular metabolism and accumulation of CD103+ DCs and alveolar macrophages in lung. Moreover, while numbers of mTOR-deficient lung CD11b+ DCs were not changed, they were metabolically reprogrammed to skew allergic inflammation from eosinophilic T helper cell 2 (TH2) to neutrophilic TH17 polarity. The mechanism for this change was independent of translational control but dependent on inflammatory DCs, which produced interleukin-23 and increased fatty acid oxidation. mTOR therefore mediates metabolic adaptation of APCs in distinct tissues, influencing the immunological character of allergic inflammation.
DOI: 10.1126/science.aaj2155
PubMed: 28798047
PubMed Central: PMC5746055
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
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wicri:level="2"><nlm:affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Benitez, Lydia" sort="Benitez, Lydia" uniqKey="Benitez L" first="Lydia" last="Benitez">Lydia Benitez</name><affiliation wicri:level="2"><nlm:affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Todor, Andrei" sort="Todor, Andrei" uniqKey="Todor A" first="Andrei" last="Todor">Andrei Todor</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, Emory University, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Emory University, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Machiah, Deepa" sort="Machiah, Deepa" uniqKey="Machiah D" first="Deepa" last="Machiah">Deepa Machiah</name><affiliation wicri:level="2"><nlm:affiliation>Yerkes Molecular Pathology Core Laboratory, Yerkes National Primate Research Center, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Yerkes Molecular Pathology Core Laboratory, Yerkes National Primate Research Center, 954 Gatewood Road NE, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Oriss, Timothy" sort="Oriss, Timothy" uniqKey="Oriss T" first="Timothy" last="Oriss">Timothy Oriss</name><affiliation wicri:level="2"><nlm:affiliation>Division of Pulmonary, Allergy and Critical Care Medicine, Department of Immunology, University of Pittsburgh Asthma Institute at University of Pittsburgh Medical Center (UPMC), University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Pulmonary, Allergy and Critical Care Medicine, Department of Immunology, University of Pittsburgh Asthma Institute at University of Pittsburgh Medical Center (UPMC), University of Pittsburgh School of Medicine, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Ray, Anuradha" sort="Ray, Anuradha" uniqKey="Ray A" first="Anuradha" last="Ray">Anuradha Ray</name><affiliation wicri:level="2"><nlm:affiliation>Division of Pulmonary, Allergy and Critical Care Medicine, Department of Immunology, University of Pittsburgh Asthma Institute at University of Pittsburgh Medical Center (UPMC), University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Pulmonary, Allergy and Critical Care Medicine, Department of Immunology, University of Pittsburgh Asthma Institute at University of Pittsburgh Medical Center (UPMC), University of Pittsburgh School of Medicine, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Bosinger, Steven" sort="Bosinger, Steven" uniqKey="Bosinger S" first="Steven" last="Bosinger">Steven Bosinger</name><affiliation wicri:level="2"><nlm:affiliation>Primate Genomics Core, Yerkes National Primate Research Center, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Primate Genomics Core, Yerkes National Primate Research Center, 954 Gatewood Road NE, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Ravindran, Rajesh" sort="Ravindran, Rajesh" uniqKey="Ravindran R" first="Rajesh" last="Ravindran">Rajesh Ravindran</name><affiliation wicri:level="2"><nlm:affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Li, Shuzhao" sort="Li, Shuzhao" uniqKey="Li S" first="Shuzhao" last="Li">Shuzhao Li</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, Emory University, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Emory University, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Pulendran, Bali" sort="Pulendran, Bali" uniqKey="Pulendran B" first="Bali" last="Pulendran">Bali Pulendran</name><affiliation wicri:level="2"><nlm:affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA. bpulend@emory.edu bpulend@stanford.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Department of Pathology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute for Immunity, Transplantation and Infection, Department of Pathology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28798047</idno><idno type="pmid">28798047</idno><idno type="doi">10.1126/science.aaj2155</idno><idno type="pmc">PMC5746055</idno><idno type="wicri:Area/Main/Corpus">000754</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000754</idno><idno type="wicri:Area/Main/Curation">000754</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000754</idno><idno type="wicri:Area/Main/Exploration">000754</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">mTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation.</title><author><name sortKey="Sinclair, Charles" sort="Sinclair, Charles" uniqKey="Sinclair C" first="Charles" last="Sinclair">Charles Sinclair</name><affiliation wicri:level="2"><nlm:affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Bommakanti, Gayathri" sort="Bommakanti, Gayathri" uniqKey="Bommakanti G" first="Gayathri" last="Bommakanti">Gayathri Bommakanti</name><affiliation wicri:level="2"><nlm:affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Gardinassi, Luiz" sort="Gardinassi, Luiz" uniqKey="Gardinassi L" first="Luiz" last="Gardinassi">Luiz Gardinassi</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, Emory University, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Emory University, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Loebbermann, Jens" sort="Loebbermann, Jens" uniqKey="Loebbermann J" first="Jens" last="Loebbermann">Jens Loebbermann</name><affiliation wicri:level="2"><nlm:affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Johnson, Matthew Joseph" sort="Johnson, Matthew Joseph" uniqKey="Johnson M" first="Matthew Joseph" last="Johnson">Matthew Joseph Johnson</name><affiliation wicri:level="2"><nlm:affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455</wicri:regionArea><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Hakimpour, Paul" sort="Hakimpour, Paul" uniqKey="Hakimpour P" first="Paul" last="Hakimpour">Paul Hakimpour</name><affiliation wicri:level="2"><nlm:affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Hagan, Thomas" sort="Hagan, Thomas" uniqKey="Hagan T" first="Thomas" last="Hagan">Thomas Hagan</name><affiliation wicri:level="2"><nlm:affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Benitez, Lydia" sort="Benitez, Lydia" uniqKey="Benitez L" first="Lydia" last="Benitez">Lydia Benitez</name><affiliation wicri:level="2"><nlm:affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Todor, Andrei" sort="Todor, Andrei" uniqKey="Todor A" first="Andrei" last="Todor">Andrei Todor</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, Emory University, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Emory University, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Machiah, Deepa" sort="Machiah, Deepa" uniqKey="Machiah D" first="Deepa" last="Machiah">Deepa Machiah</name><affiliation wicri:level="2"><nlm:affiliation>Yerkes Molecular Pathology Core Laboratory, Yerkes National Primate Research Center, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Yerkes Molecular Pathology Core Laboratory, Yerkes National Primate Research Center, 954 Gatewood Road NE, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Oriss, Timothy" sort="Oriss, Timothy" uniqKey="Oriss T" first="Timothy" last="Oriss">Timothy Oriss</name><affiliation wicri:level="2"><nlm:affiliation>Division of Pulmonary, Allergy and Critical Care Medicine, Department of Immunology, University of Pittsburgh Asthma Institute at University of Pittsburgh Medical Center (UPMC), University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Pulmonary, Allergy and Critical Care Medicine, Department of Immunology, University of Pittsburgh Asthma Institute at University of Pittsburgh Medical Center (UPMC), University of Pittsburgh School of Medicine, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Ray, Anuradha" sort="Ray, Anuradha" uniqKey="Ray A" first="Anuradha" last="Ray">Anuradha Ray</name><affiliation wicri:level="2"><nlm:affiliation>Division of Pulmonary, Allergy and Critical Care Medicine, Department of Immunology, University of Pittsburgh Asthma Institute at University of Pittsburgh Medical Center (UPMC), University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Pulmonary, Allergy and Critical Care Medicine, Department of Immunology, University of Pittsburgh Asthma Institute at University of Pittsburgh Medical Center (UPMC), University of Pittsburgh School of Medicine, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Bosinger, Steven" sort="Bosinger, Steven" uniqKey="Bosinger S" first="Steven" last="Bosinger">Steven Bosinger</name><affiliation wicri:level="2"><nlm:affiliation>Primate Genomics Core, Yerkes National Primate Research Center, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Primate Genomics Core, Yerkes National Primate Research Center, 954 Gatewood Road NE, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Ravindran, Rajesh" sort="Ravindran, Rajesh" uniqKey="Ravindran R" first="Rajesh" last="Ravindran">Rajesh Ravindran</name><affiliation wicri:level="2"><nlm:affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Li, Shuzhao" sort="Li, Shuzhao" uniqKey="Li S" first="Shuzhao" last="Li">Shuzhao Li</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, Emory University, Atlanta, GA 30329, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Emory University, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Pulendran, Bali" sort="Pulendran, Bali" uniqKey="Pulendran B" first="Bali" last="Pulendran">Bali Pulendran</name><affiliation wicri:level="2"><nlm:affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA. bpulend@emory.edu bpulend@stanford.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Institute for Immunity, Transplantation and Infection, Department of Pathology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute for Immunity, Transplantation and Infection, Department of Pathology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author></analytic><series><title level="j">Science (New York, N.Y.)</title><idno type="eISSN">1095-9203</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Antigen Presentation (MeSH)</term><term>Antigens, CD (metabolism)</term><term>CD11b Antigen (genetics)</term><term>CD11b Antigen (metabolism)</term><term>Dendritic Cells (immunology)</term><term>Eosinophils (immunology)</term><term>Fatty Acids (metabolism)</term><term>Homeostasis (MeSH)</term><term>Hypersensitivity (metabolism)</term><term>Inflammation (metabolism)</term><term>Integrin alpha Chains (metabolism)</term><term>Interleukin-23 (metabolism)</term><term>Lung (metabolism)</term><term>Lung (pathology)</term><term>Mice (MeSH)</term><term>Mice, Inbred C57BL (MeSH)</term><term>Neutrophils (immunology)</term><term>Oxidation-Reduction (MeSH)</term><term>TOR Serine-Threonine Kinases (genetics)</term><term>TOR Serine-Threonine Kinases (metabolism)</term><term>Th17 Cells (immunology)</term><term>Th2 Cells (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acides gras (métabolisme)</term><term>Animaux (MeSH)</term><term>Antigènes CD (métabolisme)</term><term>Antigènes CD11b (génétique)</term><term>Antigènes CD11b (métabolisme)</term><term>Cellules Th17 (immunologie)</term><term>Cellules dendritiques (immunologie)</term><term>Granulocytes neutrophiles (immunologie)</term><term>Granulocytes éosinophiles (immunologie)</term><term>Homéostasie (MeSH)</term><term>Hypersensibilité (métabolisme)</term><term>Inflammation (métabolisme)</term><term>Interleukine-23 (métabolisme)</term><term>Intégrines alpha (métabolisme)</term><term>Lymphocytes auxiliaires Th2 (immunologie)</term><term>Oxydoréduction (MeSH)</term><term>Poumon (anatomopathologie)</term><term>Poumon (métabolisme)</term><term>Présentation d'antigène (MeSH)</term><term>Souris (MeSH)</term><term>Souris de lignée C57BL (MeSH)</term><term>Sérine-thréonine kinases TOR (génétique)</term><term>Sérine-thréonine kinases TOR (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>CD11b Antigen</term><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antigens, CD</term><term>CD11b Antigen</term><term>Fatty Acids</term><term>Integrin alpha Chains</term><term>Interleukin-23</term><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Antigènes CD11b</term><term>Sérine-thréonine kinases TOR</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Cellules Th17</term><term>Cellules dendritiques</term><term>Granulocytes neutrophiles</term><term>Granulocytes éosinophiles</term><term>Lymphocytes auxiliaires Th2</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Dendritic Cells</term><term>Eosinophils</term><term>Neutrophils</term><term>Th17 Cells</term><term>Th2 Cells</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Hypersensitivity</term><term>Inflammation</term><term>Lung</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Acides gras</term><term>Antigènes CD</term><term>Antigènes CD11b</term><term>Hypersensibilité</term><term>Inflammation</term><term>Interleukine-23</term><term>Intégrines alpha</term><term>Poumon</term><term>Sérine-thréonine kinases TOR</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Antigen Presentation</term><term>Homeostasis</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Oxidation-Reduction</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Homéostasie</term><term>Oxydoréduction</term><term>Présentation d'antigène</term><term>Souris</term><term>Souris de lignée C57BL</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Antigen-presenting cells (APCs) occupy diverse anatomical tissues, but their tissue-restricted homeostasis remains poorly understood. Here, working with mouse models of inflammation, we found that mechanistic target of rapamycin (mTOR)-dependent metabolic adaptation was required at discrete locations. mTOR was dispensable for dendritic cell (DC) homeostasis in secondary lymphoid tissues but necessary to regulate cellular metabolism and accumulation of CD103<sup>+</sup> DCs and alveolar macrophages in lung. Moreover, while numbers of mTOR-deficient lung CD11b<sup>+</sup> DCs were not changed, they were metabolically reprogrammed to skew allergic inflammation from eosinophilic T helper cell 2 (T<sub>H</sub>2) to neutrophilic T<sub>H</sub>17 polarity. The mechanism for this change was independent of translational control but dependent on inflammatory DCs, which produced interleukin-23 and increased fatty acid oxidation. mTOR therefore mediates metabolic adaptation of APCs in distinct tissues, influencing the immunological character of allergic inflammation.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28798047</PMID><DateCompleted><Year>2018</Year><Month>03</Month><Day>06</Day></DateCompleted><DateRevised><Year>2019</Year><Month>09</Month><Day>25</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1095-9203</ISSN><JournalIssue CitedMedium="Internet"><Volume>357</Volume><Issue>6355</Issue><PubDate><Year>2017</Year><Month>09</Month><Day>08</Day></PubDate></JournalIssue><Title>Science (New York, N.Y.)</Title><ISOAbbreviation>Science</ISOAbbreviation></Journal><ArticleTitle>mTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation.</ArticleTitle><Pagination><MedlinePgn>1014-1021</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1126/science.aaj2155</ELocationID><Abstract><AbstractText>Antigen-presenting cells (APCs) occupy diverse anatomical tissues, but their tissue-restricted homeostasis remains poorly understood. Here, working with mouse models of inflammation, we found that mechanistic target of rapamycin (mTOR)-dependent metabolic adaptation was required at discrete locations. mTOR was dispensable for dendritic cell (DC) homeostasis in secondary lymphoid tissues but necessary to regulate cellular metabolism and accumulation of CD103<sup>+</sup> DCs and alveolar macrophages in lung. Moreover, while numbers of mTOR-deficient lung CD11b<sup>+</sup> DCs were not changed, they were metabolically reprogrammed to skew allergic inflammation from eosinophilic T helper cell 2 (T<sub>H</sub>2) to neutrophilic T<sub>H</sub>17 polarity. The mechanism for this change was independent of translational control but dependent on inflammatory DCs, which produced interleukin-23 and increased fatty acid oxidation. mTOR therefore mediates metabolic adaptation of APCs in distinct tissues, influencing the immunological character of allergic inflammation.</AbstractText><CopyrightInformation>Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sinclair</LastName><ForeName>Charles</ForeName><Initials>C</Initials><Identifier Source="ORCID">0000-0001-6857-9993</Identifier><AffiliationInfo><Affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bommakanti</LastName><ForeName>Gayathri</ForeName><Initials>G</Initials><Identifier Source="ORCID">0000-0002-3420-2802</Identifier><AffiliationInfo><Affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gardinassi</LastName><ForeName>Luiz</ForeName><Initials>L</Initials><Identifier Source="ORCID">0000-0002-9027-2688</Identifier><AffiliationInfo><Affiliation>Department of Medicine, Emory University, Atlanta, GA 30329, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Loebbermann</LastName><ForeName>Jens</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0003-1439-0073</Identifier><AffiliationInfo><Affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Johnson</LastName><ForeName>Matthew Joseph</ForeName><Initials>MJ</Initials><Identifier Source="ORCID">0000-0002-1313-1742</Identifier><AffiliationInfo><Affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hakimpour</LastName><ForeName>Paul</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hagan</LastName><ForeName>Thomas</ForeName><Initials>T</Initials><Identifier Source="ORCID">0000-0002-5254-5251</Identifier><AffiliationInfo><Affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Benitez</LastName><ForeName>Lydia</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Todor</LastName><ForeName>Andrei</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Medicine, Emory University, Atlanta, GA 30329, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Machiah</LastName><ForeName>Deepa</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Yerkes Molecular Pathology Core Laboratory, Yerkes National Primate Research Center, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oriss</LastName><ForeName>Timothy</ForeName><Initials>T</Initials><Identifier Source="ORCID">0000-0002-9725-9996</Identifier><AffiliationInfo><Affiliation>Division of Pulmonary, Allergy and Critical Care Medicine, Department of Immunology, University of Pittsburgh Asthma Institute at University of Pittsburgh Medical Center (UPMC), University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ray</LastName><ForeName>Anuradha</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Division of Pulmonary, Allergy and Critical Care Medicine, Department of Immunology, University of Pittsburgh Asthma Institute at University of Pittsburgh Medical Center (UPMC), University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bosinger</LastName><ForeName>Steven</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Primate Genomics Core, Yerkes National Primate Research Center, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ravindran</LastName><ForeName>Rajesh</ForeName><Initials>R</Initials><Identifier Source="ORCID">0000-0002-1357-2564</Identifier><AffiliationInfo><Affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Shuzhao</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Medicine, Emory University, Atlanta, GA 30329, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pulendran</LastName><ForeName>Bali</ForeName><Initials>B</Initials><Identifier Source="ORCID">0000-0001-6517-4333</Identifier><AffiliationInfo><Affiliation>Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA. bpulend@emory.edu bpulend@stanford.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute for Immunity, Transplantation and Infection, Department of Pathology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R37 DK057665</GrantID><Acronym>DK</Acronym><Agency>NIDDK NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P51 OD011132</GrantID><Acronym>OD</Acronym><Agency>NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R37 AI048638</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>U19 AI057266</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32 AI007290</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>U19 AI090023</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>08</Month><Day>10</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Science</MedlineTA><NlmUniqueID>0404511</NlmUniqueID><ISSNLinking>0036-8075</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015703">Antigens, CD</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D039481">CD11b Antigen</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D005227">Fatty Acids</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D039001">Integrin alpha Chains</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D053759">Interleukin-23</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C091367">alpha E integrins</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber><NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber><NameOfSubstance UI="C546843">mTOR protein, mouse</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>Science. 2017 Sep 8;357(6355):973-974</RefSource><PMID Version="1">28883060</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017951" MajorTopicYN="N">Antigen Presentation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015703" MajorTopicYN="N">Antigens, CD</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D039481" MajorTopicYN="N">CD11b Antigen</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003713" MajorTopicYN="N">Dendritic Cells</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004804" MajorTopicYN="N">Eosinophils</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005227" MajorTopicYN="N">Fatty Acids</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006706" MajorTopicYN="Y">Homeostasis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006967" MajorTopicYN="N">Hypersensitivity</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007249" MajorTopicYN="N">Inflammation</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D039001" MajorTopicYN="N">Integrin alpha Chains</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053759" MajorTopicYN="N">Interleukin-23</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008168" MajorTopicYN="N">Lung</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009504" MajorTopicYN="N">Neutrophils</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010084" MajorTopicYN="N">Oxidation-Reduction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D058504" MajorTopicYN="N">Th17 Cells</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018418" MajorTopicYN="N">Th2 Cells</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>09</Month><Day>14</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2017</Year><Month>03</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2017</Year><Month>06</Month><Day>22</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>8</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018</Year><Month>3</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>8</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28798047</ArticleId><ArticleId IdType="pii">science.aaj2155</ArticleId><ArticleId IdType="doi">10.1126/science.aaj2155</ArticleId><ArticleId IdType="pmc">PMC5746055</ArticleId><ArticleId IdType="mid">NIHMS929362</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Immunity. 2008 Oct 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Deepa" sort="Machiah, Deepa" uniqKey="Machiah D" first="Deepa" last="Machiah">Deepa Machiah</name><name sortKey="Oriss, Timothy" sort="Oriss, Timothy" uniqKey="Oriss T" first="Timothy" last="Oriss">Timothy Oriss</name><name sortKey="Pulendran, Bali" sort="Pulendran, Bali" uniqKey="Pulendran B" first="Bali" last="Pulendran">Bali Pulendran</name><name sortKey="Pulendran, Bali" sort="Pulendran, Bali" uniqKey="Pulendran B" first="Bali" last="Pulendran">Bali Pulendran</name><name sortKey="Pulendran, Bali" sort="Pulendran, Bali" uniqKey="Pulendran B" first="Bali" last="Pulendran">Bali Pulendran</name><name sortKey="Ravindran, Rajesh" sort="Ravindran, Rajesh" uniqKey="Ravindran R" first="Rajesh" last="Ravindran">Rajesh Ravindran</name><name sortKey="Ray, Anuradha" sort="Ray, Anuradha" uniqKey="Ray A" first="Anuradha" last="Ray">Anuradha Ray</name><name sortKey="Todor, Andrei" sort="Todor, Andrei" uniqKey="Todor A" first="Andrei" last="Todor">Andrei 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