RapamycinFungusV1, Main, Exploration, bibRecord, 000956

mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation.

Identifieur interne : 000956 ( Main/Exploration ); précédent : 000955; suivant : 000957

mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation.

Auteurs : Hu Zeng [États-Unis] ; Sivan Cohen [États-Unis] ; Cliff Guy [États-Unis] ; Sharad Shrestha [États-Unis] ; Geoffrey Neale [États-Unis] ; Scott A. Brown [États-Unis] ; Caryn Cloer [États-Unis] ; Rigel J. Kishton [États-Unis] ; Xia Gao [États-Unis] ; Ben Youngblood [États-Unis] ; Mytrang Do [États-Unis] ; Ming O. Li [États-Unis] ; Jason W. Locasale [États-Unis] ; Jeffrey C. Rathmell [États-Unis] ; Hongbo Chi [États-Unis]

Source :

Immunity [ 1097-4180 ] ; 2016.

RBID : pubmed:27637146

Descripteurs français

English descriptors

KwdEn :
- Animals (MeSH), CD4-Positive T-Lymphocytes (immunology), CD4-Positive T-Lymphocytes (metabolism), Cell Differentiation (immunology), Cells, Cultured (MeSH), Germinal Center (immunology), Germinal Center (metabolism), Glucose (metabolism), Immunity, Humoral (immunology), Lymphocyte Activation (immunology), Mechanistic Target of Rapamycin Complex 1 (MeSH), Mechanistic Target of Rapamycin Complex 2 (MeSH), Mice (MeSH), Mice, Inbred C57BL (MeSH), Multiprotein Complexes (immunology), Multiprotein Complexes (metabolism), Signal Transduction (immunology), T-Lymphocytes, Helper-Inducer (immunology), T-Lymphocytes, Helper-Inducer (metabolism), TOR Serine-Threonine Kinases (immunology), TOR Serine-Threonine Kinases (metabolism).
MESH :
- chemical , immunology : Multiprotein Complexes, TOR Serine-Threonine Kinases.
- chemical , metabolism : Glucose, Multiprotein Complexes, TOR Serine-Threonine Kinases.
- immunology : CD4-Positive T-Lymphocytes, Cell Differentiation, Germinal Center, Immunity, Humoral, Lymphocyte Activation, Signal Transduction, T-Lymphocytes, Helper-Inducer.
- metabolism : CD4-Positive T-Lymphocytes, Germinal Center, T-Lymphocytes, Helper-Inducer.
- Animals, Cells, Cultured, Mechanistic Target of Rapamycin Complex 1, Mechanistic Target of Rapamycin Complex 2, Mice, Mice, Inbred C57BL.

Abstract

Follicular helper T (Tfh) cells are crucial for germinal center (GC) formation and humoral adaptive immunity. Mechanisms underlying Tfh cell differentiation in peripheral and mucosal lymphoid organs are incompletely understood. We report here that mTOR kinase complexes 1 and 2 (mTORC1 and mTORC2) are essential for Tfh cell differentiation and GC reaction under steady state and after antigen immunization and viral infection. Loss of mTORC1 and mTORC2 in T cells exerted distinct effects on Tfh cell signature gene expression, whereas increased mTOR activity promoted Tfh responses. Deficiency of mTORC2 impaired CD4(+) T cell accumulation and immunoglobulin A production and aberrantly induced the transcription factor Foxo1. Mechanistically, the costimulatory molecule ICOS activated mTORC1 and mTORC2 to drive glycolysis and lipogenesis, and glucose transporter 1-mediated glucose metabolism promoted Tfh cell responses. Altogether, mTOR acts as a central node in Tfh cells by linking immune signals to anabolic metabolism and transcriptional activity.

DOI: 10.1016/j.immuni.2016.08.017
PubMed: 27637146
PubMed Central: PMC5050556

Affiliations:

Links toward previous steps (curation, corpus...)

to stream Main, to step Corpus: 000970
to stream Main, to step Curation: 000970

Le document en format XML

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<author><name sortKey="Brown, Scott A" sort="Brown, Scott A" uniqKey="Brown S" first="Scott A" last="Brown">Scott A. Brown</name>
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<author><name sortKey="Cloer, Caryn" sort="Cloer, Caryn" uniqKey="Cloer C" first="Caryn" last="Cloer">Caryn Cloer</name>
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</placeName>
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<wicri:regionArea>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
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<author><name sortKey="Gao, Xia" sort="Gao, Xia" uniqKey="Gao X" first="Xia" last="Gao">Xia Gao</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
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<author><name sortKey="Youngblood, Ben" sort="Youngblood, Ben" uniqKey="Youngblood B" first="Ben" last="Youngblood">Ben Youngblood</name>
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<author><name sortKey="Do, Mytrang" sort="Do, Mytrang" uniqKey="Do M" first="Mytrang" last="Do">Mytrang Do</name>
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</placeName>
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<author><name sortKey="Li, Ming O" sort="Li, Ming O" uniqKey="Li M" first="Ming O" last="Li">Ming O. Li</name>
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<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
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<author><name sortKey="Locasale, Jason W" sort="Locasale, Jason W" uniqKey="Locasale J" first="Jason W" last="Locasale">Jason W. Locasale</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rathmell, Jeffrey C" sort="Rathmell, Jeffrey C" uniqKey="Rathmell J" first="Jeffrey C" last="Rathmell">Jeffrey C. Rathmell</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA; Department of Pathology, Microbiology, and Immunology, and Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN 37232</wicri:regionArea>
<placeName><region type="state">Tennessee</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chi, Hongbo" sort="Chi, Hongbo" uniqKey="Chi H" first="Hongbo" last="Chi">Hongbo Chi</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: hongbo.chi@stjude.org.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105</wicri:regionArea>
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</affiliation>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation.</title>
<author><name sortKey="Zeng, Hu" sort="Zeng, Hu" uniqKey="Zeng H" first="Hu" last="Zeng">Hu Zeng</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105</wicri:regionArea>
<placeName><region type="state">Tennessee</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cohen, Sivan" sort="Cohen, Sivan" uniqKey="Cohen S" first="Sivan" last="Cohen">Sivan Cohen</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Guy, Cliff" sort="Guy, Cliff" uniqKey="Guy C" first="Cliff" last="Guy">Cliff Guy</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105</wicri:regionArea>
<placeName><region type="state">Tennessee</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shrestha, Sharad" sort="Shrestha, Sharad" uniqKey="Shrestha S" first="Sharad" last="Shrestha">Sharad Shrestha</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105</wicri:regionArea>
<placeName><region type="state">Tennessee</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Neale, Geoffrey" sort="Neale, Geoffrey" uniqKey="Neale G" first="Geoffrey" last="Neale">Geoffrey Neale</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, TN 38105</wicri:regionArea>
<placeName><region type="state">Tennessee</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Brown, Scott A" sort="Brown, Scott A" uniqKey="Brown S" first="Scott A" last="Brown">Scott A. Brown</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105</wicri:regionArea>
<placeName><region type="state">Tennessee</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cloer, Caryn" sort="Cloer, Caryn" uniqKey="Cloer C" first="Caryn" last="Cloer">Caryn Cloer</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105</wicri:regionArea>
<placeName><region type="state">Tennessee</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kishton, Rigel J" sort="Kishton, Rigel J" uniqKey="Kishton R" first="Rigel J" last="Kishton">Rigel J. Kishton</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gao, Xia" sort="Gao, Xia" uniqKey="Gao X" first="Xia" last="Gao">Xia Gao</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Youngblood, Ben" sort="Youngblood, Ben" uniqKey="Youngblood B" first="Ben" last="Youngblood">Ben Youngblood</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105</wicri:regionArea>
<placeName><region type="state">Tennessee</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Do, Mytrang" sort="Do, Mytrang" uniqKey="Do M" first="Mytrang" last="Do">Mytrang Do</name>
<affiliation wicri:level="2"><nlm:affiliation>Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Li, Ming O" sort="Li, Ming O" uniqKey="Li M" first="Ming O" last="Li">Ming O. Li</name>
<affiliation wicri:level="2"><nlm:affiliation>Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Locasale, Jason W" sort="Locasale, Jason W" uniqKey="Locasale J" first="Jason W" last="Locasale">Jason W. Locasale</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rathmell, Jeffrey C" sort="Rathmell, Jeffrey C" uniqKey="Rathmell J" first="Jeffrey C" last="Rathmell">Jeffrey C. Rathmell</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA; Department of Pathology, Microbiology, and Immunology, and Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: jeff.rathmell@vanderbilt.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA; Department of Pathology, Microbiology, and Immunology, and Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN 37232</wicri:regionArea>
<placeName><region type="state">Tennessee</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chi, Hongbo" sort="Chi, Hongbo" uniqKey="Chi H" first="Hongbo" last="Chi">Hongbo Chi</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: hongbo.chi@stjude.org.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105</wicri:regionArea>
<placeName><region type="state">Tennessee</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Immunity</title>
<idno type="eISSN">1097-4180</idno>
<imprint><date when="2016" type="published">2016</date>
</imprint>
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</sourceDesc>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term>
<term>CD4-Positive T-Lymphocytes (immunology)</term>
<term>CD4-Positive T-Lymphocytes (metabolism)</term>
<term>Cell Differentiation (immunology)</term>
<term>Cells, Cultured (MeSH)</term>
<term>Germinal Center (immunology)</term>
<term>Germinal Center (metabolism)</term>
<term>Glucose (metabolism)</term>
<term>Immunity, Humoral (immunology)</term>
<term>Lymphocyte Activation (immunology)</term>
<term>Mechanistic Target of Rapamycin Complex 1 (MeSH)</term>
<term>Mechanistic Target of Rapamycin Complex 2 (MeSH)</term>
<term>Mice (MeSH)</term>
<term>Mice, Inbred C57BL (MeSH)</term>
<term>Multiprotein Complexes (immunology)</term>
<term>Multiprotein Complexes (metabolism)</term>
<term>Signal Transduction (immunology)</term>
<term>T-Lymphocytes, Helper-Inducer (immunology)</term>
<term>T-Lymphocytes, Helper-Inducer (metabolism)</term>
<term>TOR Serine-Threonine Kinases (immunology)</term>
<term>TOR Serine-Threonine Kinases (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Activation des lymphocytes (immunologie)</term>
<term>Animaux (MeSH)</term>
<term>Cellules cultivées (MeSH)</term>
<term>Centre germinatif (immunologie)</term>
<term>Centre germinatif (métabolisme)</term>
<term>Complexe-1 cible mécanistique de la rapamycine (MeSH)</term>
<term>Complexe-2 cible mécanistique de la rapamycine (MeSH)</term>
<term>Complexes multiprotéiques (immunologie)</term>
<term>Complexes multiprotéiques (métabolisme)</term>
<term>Différenciation cellulaire (immunologie)</term>
<term>Glucose (métabolisme)</term>
<term>Immunité humorale (immunologie)</term>
<term>Lymphocytes T CD4+ (immunologie)</term>
<term>Lymphocytes T CD4+ (métabolisme)</term>
<term>Lymphocytes T auxiliaires (immunologie)</term>
<term>Lymphocytes T auxiliaires (métabolisme)</term>
<term>Souris (MeSH)</term>
<term>Souris de lignée C57BL (MeSH)</term>
<term>Sérine-thréonine kinases TOR (immunologie)</term>
<term>Sérine-thréonine kinases TOR (métabolisme)</term>
<term>Transduction du signal (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Multiprotein Complexes</term>
<term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Glucose</term>
<term>Multiprotein Complexes</term>
<term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Activation des lymphocytes</term>
<term>Centre germinatif</term>
<term>Complexes multiprotéiques</term>
<term>Différenciation cellulaire</term>
<term>Immunité humorale</term>
<term>Lymphocytes T CD4+</term>
<term>Lymphocytes T auxiliaires</term>
<term>Sérine-thréonine kinases TOR</term>
<term>Transduction du signal</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term>
<term>Cell Differentiation</term>
<term>Germinal Center</term>
<term>Immunity, Humoral</term>
<term>Lymphocyte Activation</term>
<term>Signal Transduction</term>
<term>T-Lymphocytes, Helper-Inducer</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term>
<term>Germinal Center</term>
<term>T-Lymphocytes, Helper-Inducer</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Centre germinatif</term>
<term>Complexes multiprotéiques</term>
<term>Glucose</term>
<term>Lymphocytes T CD4+</term>
<term>Lymphocytes T auxiliaires</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Cells, Cultured</term>
<term>Mechanistic Target of Rapamycin Complex 1</term>
<term>Mechanistic Target of Rapamycin Complex 2</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cellules cultivées</term>
<term>Complexe-1 cible mécanistique de la rapamycine</term>
<term>Complexe-2 cible mécanistique de la rapamycine</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
</keywords>
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<front><div type="abstract" xml:lang="en">Follicular helper T (Tfh) cells are crucial for germinal center (GC) formation and humoral adaptive immunity. Mechanisms underlying Tfh cell differentiation in peripheral and mucosal lymphoid organs are incompletely understood. We report here that mTOR kinase complexes 1 and 2 (mTORC1 and mTORC2) are essential for Tfh cell differentiation and GC reaction under steady state and after antigen immunization and viral infection. Loss of mTORC1 and mTORC2 in T cells exerted distinct effects on Tfh cell signature gene expression, whereas increased mTOR activity promoted Tfh responses. Deficiency of mTORC2 impaired CD4(+) T cell accumulation and immunoglobulin A production and aberrantly induced the transcription factor Foxo1. Mechanistically, the costimulatory molecule ICOS activated mTORC1 and mTORC2 to drive glycolysis and lipogenesis, and glucose transporter 1-mediated glucose metabolism promoted Tfh cell responses. Altogether, mTOR acts as a central node in Tfh cells by linking immune signals to anabolic metabolism and transcriptional activity.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27637146</PMID>
<DateCompleted><Year>2017</Year>
<Month>09</Month>
<Day>05</Day>
</DateCompleted>
<DateRevised><Year>2018</Year>
<Month>11</Month>
<Day>13</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1097-4180</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>45</Volume>
<Issue>3</Issue>
<PubDate><Year>2016</Year>
<Month>09</Month>
<Day>20</Day>
</PubDate>
</JournalIssue>
<Title>Immunity</Title>
<ISOAbbreviation>Immunity</ISOAbbreviation>
</Journal>
<ArticleTitle>mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation.</ArticleTitle>
<Pagination><MedlinePgn>540-554</MedlinePgn>
</Pagination>
<ELocationID EIdType="pii" ValidYN="Y">S1074-7613(16)30341-7</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.immuni.2016.08.017</ELocationID>
<Abstract><AbstractText>Follicular helper T (Tfh) cells are crucial for germinal center (GC) formation and humoral adaptive immunity. Mechanisms underlying Tfh cell differentiation in peripheral and mucosal lymphoid organs are incompletely understood. We report here that mTOR kinase complexes 1 and 2 (mTORC1 and mTORC2) are essential for Tfh cell differentiation and GC reaction under steady state and after antigen immunization and viral infection. Loss of mTORC1 and mTORC2 in T cells exerted distinct effects on Tfh cell signature gene expression, whereas increased mTOR activity promoted Tfh responses. Deficiency of mTORC2 impaired CD4(+) T cell accumulation and immunoglobulin A production and aberrantly induced the transcription factor Foxo1. Mechanistically, the costimulatory molecule ICOS activated mTORC1 and mTORC2 to drive glycolysis and lipogenesis, and glucose transporter 1-mediated glucose metabolism promoted Tfh cell responses. Altogether, mTOR acts as a central node in Tfh cells by linking immune signals to anabolic metabolism and transcriptional activity.</AbstractText>
<CopyrightInformation>Copyright © 2016 Elsevier Inc. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zeng</LastName>
<ForeName>Hu</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cohen</LastName>
<ForeName>Sivan</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Guy</LastName>
<ForeName>Cliff</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Shrestha</LastName>
<ForeName>Sharad</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Neale</LastName>
<ForeName>Geoffrey</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Brown</LastName>
<ForeName>Scott A</ForeName>
<Initials>SA</Initials>
<AffiliationInfo><Affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cloer</LastName>
<ForeName>Caryn</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kishton</LastName>
<ForeName>Rigel J</ForeName>
<Initials>RJ</Initials>
<AffiliationInfo><Affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gao</LastName>
<ForeName>Xia</ForeName>
<Initials>X</Initials>
<AffiliationInfo><Affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Youngblood</LastName>
<ForeName>Ben</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Do</LastName>
<ForeName>Mytrang</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Li</LastName>
<ForeName>Ming O</ForeName>
<Initials>MO</Initials>
<AffiliationInfo><Affiliation>Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Locasale</LastName>
<ForeName>Jason W</ForeName>
<Initials>JW</Initials>
<AffiliationInfo><Affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Rathmell</LastName>
<ForeName>Jeffrey C</ForeName>
<Initials>JC</Initials>
<AffiliationInfo><Affiliation>Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA; Department of Pathology, Microbiology, and Immunology, and Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: jeff.rathmell@vanderbilt.edu.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chi</LastName>
<ForeName>Hongbo</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: hongbo.chi@stjude.org.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>R01 CA193256</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>F31 CA183529</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 DK105550</GrantID>
<Acronym>DK</Acronym>
<Agency>NIDDK NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>P30 CA008748</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R00 CA168997</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 NS064599</GrantID>
<Acronym>NS</Acronym>
<Agency>NINDS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 AI105887</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 CA176624</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 AI101407</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>2016</Year>
<Month>09</Month>
<Day>13</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Immunity</MedlineTA>
<NlmUniqueID>9432918</NlmUniqueID>
<ISSNLinking>1074-7613</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D046912">Multiprotein Complexes</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber>
<NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber>
<NameOfSubstance UI="D000076222">Mechanistic Target of Rapamycin Complex 1</NameOfSubstance>
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<Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber>
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<Chemical><RegistryNumber>IY9XDZ35W2</RegistryNumber>
<NameOfSubstance UI="D005947">Glucose</NameOfSubstance>
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<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015496" MajorTopicYN="N">CD4-Positive T-Lymphocytes</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002454" MajorTopicYN="N">Cell Differentiation</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018858" MajorTopicYN="N">Germinal Center</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005947" MajorTopicYN="N">Glucose</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D056724" MajorTopicYN="N">Immunity, Humoral</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008213" MajorTopicYN="N">Lymphocyte Activation</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000076222" MajorTopicYN="N">Mechanistic Target of Rapamycin Complex 1</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000076225" MajorTopicYN="N">Mechanistic Target of Rapamycin Complex 2</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D046912" MajorTopicYN="N">Multiprotein Complexes</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006377" MajorTopicYN="N">T-Lymphocytes, Helper-Inducer</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
</MeshHeadingList>
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<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Caroline du Nord</li>
<li>Tennessee</li>
<li>État de New York</li>
</region>
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<tree><country name="États-Unis"><region name="Tennessee"><name sortKey="Zeng, Hu" sort="Zeng, Hu" uniqKey="Zeng H" first="Hu" last="Zeng">Hu Zeng</name>
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<name sortKey="Brown, Scott A" sort="Brown, Scott A" uniqKey="Brown S" first="Scott A" last="Brown">Scott A. Brown</name>
<name sortKey="Chi, Hongbo" sort="Chi, Hongbo" uniqKey="Chi H" first="Hongbo" last="Chi">Hongbo Chi</name>
<name sortKey="Cloer, Caryn" sort="Cloer, Caryn" uniqKey="Cloer C" first="Caryn" last="Cloer">Caryn Cloer</name>
<name sortKey="Cohen, Sivan" sort="Cohen, Sivan" uniqKey="Cohen S" first="Sivan" last="Cohen">Sivan Cohen</name>
<name sortKey="Do, Mytrang" sort="Do, Mytrang" uniqKey="Do M" first="Mytrang" last="Do">Mytrang Do</name>
<name sortKey="Gao, Xia" sort="Gao, Xia" uniqKey="Gao X" first="Xia" last="Gao">Xia Gao</name>
<name sortKey="Guy, Cliff" sort="Guy, Cliff" uniqKey="Guy C" first="Cliff" last="Guy">Cliff Guy</name>
<name sortKey="Kishton, Rigel J" sort="Kishton, Rigel J" uniqKey="Kishton R" first="Rigel J" last="Kishton">Rigel J. Kishton</name>
<name sortKey="Li, Ming O" sort="Li, Ming O" uniqKey="Li M" first="Ming O" last="Li">Ming O. Li</name>
<name sortKey="Locasale, Jason W" sort="Locasale, Jason W" uniqKey="Locasale J" first="Jason W" last="Locasale">Jason W. Locasale</name>
<name sortKey="Neale, Geoffrey" sort="Neale, Geoffrey" uniqKey="Neale G" first="Geoffrey" last="Neale">Geoffrey Neale</name>
<name sortKey="Rathmell, Jeffrey C" sort="Rathmell, Jeffrey C" uniqKey="Rathmell J" first="Jeffrey C" last="Rathmell">Jeffrey C. Rathmell</name>
<name sortKey="Shrestha, Sharad" sort="Shrestha, Sharad" uniqKey="Shrestha S" first="Sharad" last="Shrestha">Sharad Shrestha</name>
<name sortKey="Youngblood, Ben" sort="Youngblood, Ben" uniqKey="Youngblood B" first="Ben" last="Youngblood">Ben Youngblood</name>
</country>
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</record>

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HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000956 | SxmlIndent | more

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{{Explor lien
   |wiki=    Bois
   |area=    RapamycinFungusV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     pubmed:27637146
   |texte=   mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation.
}}

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	Serveur d'exploration sur la rapamycine et les champignons
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

Serveur d'exploration sur la rapamycine et les champignons

mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation.

mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation.

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