RapamycinFungusV1, Main, Exploration, bibRecord, 000701

Tsc1 expression by dendritic cells is required to preserve T-cell homeostasis and response.

Identifieur interne : 000701 ( Main/Exploration ); précédent : 000700; suivant : 000702

Tsc1 expression by dendritic cells is required to preserve T-cell homeostasis and response.

Source :

Cell death & disease [ 2041-4889 ] ; 2017.

RBID : pubmed:28079897

Descripteurs français

English descriptors

KwdEn :
- Animals (MeSH), Cell Differentiation (genetics), Dendritic Cells (immunology), Dendritic Cells (metabolism), Dendritic Cells (pathology), Homeostasis (MeSH), Humans (MeSH), Lymphoproliferative Disorders (genetics), Lymphoproliferative Disorders (immunology), Lymphoproliferative Disorders (pathology), Mechanistic Target of Rapamycin Complex 1 (MeSH), Mice (MeSH), Multiprotein Complexes (genetics), Signal Transduction (genetics), T-Lymphocytes (immunology), T-Lymphocytes (metabolism), T-Lymphocytes (pathology), TOR Serine-Threonine Kinases (biosynthesis), TOR Serine-Threonine Kinases (genetics), Tuberous Sclerosis Complex 1 Protein (MeSH), Tumor Suppressor Proteins (biosynthesis), Tumor Suppressor Proteins (genetics), Tumor Suppressor Proteins (immunology).
MESH :
- chemical , biosynthesis : TOR Serine-Threonine Kinases, Tumor Suppressor Proteins.
- chemical , genetics : Multiprotein Complexes, TOR Serine-Threonine Kinases, Tumor Suppressor Proteins.
- chemical , immunology : Tumor Suppressor Proteins.
- chemical : Mechanistic Target of Rapamycin Complex 1, Tuberous Sclerosis Complex 1 Protein.
- genetics : Cell Differentiation, Lymphoproliferative Disorders, Signal Transduction.
- immunology : Dendritic Cells, Lymphoproliferative Disorders, T-Lymphocytes.
- metabolism : Dendritic Cells, T-Lymphocytes.
- pathology : Dendritic Cells, Lymphoproliferative Disorders, T-Lymphocytes.
- Animals, Homeostasis, Humans, Mice.

Abstract

Dendritic cells (DCs) are pivotal to the induction of adaptive T-cell immune responses. Recent evidence highlights a critical role of tuberous sclerosis complex 1 (Tsc1), a primarily upstream negative regulator of mammalian target of rapamycin (mTOR), in DC development, but whether and how Tsc1 directly regulate mature DC function in vivo remains elusive. Here we show that selective disruption of Tsc1 in DCs results in a lymphoproliferative disorder with the spontaneous activation of T cells. Tsc1 deficiency results in the activation of mTORC1-PPARγ pathway, which leads to the upregulation of neuropilin-1 (Nrp1) expression on DCs to stimulate naive T-cell proliferation. However, Tsc1-deficient DCs have defects in the ability to induce antigen-specific T-cell responses in vitro and in vivo owing to impaired survival during antigen transportation and presentation. Indeed, Tsc1 promotes DC survival through restraining independent mTORC1 and ROS-Bim pathways. Our study identifies Tsc1 as a crucial signaling checkpoint in DCs essential for preserving T-cell homeostasis and response.

DOI: 10.1038/cddis.2016.487
PubMed: 28079897
PubMed Central: PMC5386387

Affiliations:

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

to stream Main, to step Corpus: 000898
to stream Main, to step Curation: 000898

Le document en format XML

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<author><name sortKey="Cheng, Tao" sort="Cheng, Tao" uniqKey="Cheng T" first="Tao" last="Cheng">Tao Cheng</name>
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<author><name sortKey="Liao, Fang" sort="Liao, Fang" uniqKey="Liao F" first="Fang" last="Liao">Fang Liao</name>
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<wicri:regionArea>Department of Medical Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea>
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<wicri:noRegion>Jiangxi 33000</wicri:noRegion>
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<author><name sortKey="Feng, Xiaoming" sort="Feng, Xiaoming" uniqKey="Feng X" first="Xiaoming" last="Feng">Xiaoming Feng</name>
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<country xml:lang="fr">République populaire de Chine</country>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Tsc1 expression by dendritic cells is required to preserve T-cell homeostasis and response.</title>
<author><name sortKey="Luo, Yuechen" sort="Luo, Yuechen" uniqKey="Luo Y" first="Yuechen" last="Luo">Yuechen Luo</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020</wicri:regionArea>
<placeName><settlement type="city">Tianjin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Li, Wenwen" sort="Li, Wenwen" uniqKey="Li W" first="Wenwen" last="Li">Wenwen Li</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020</wicri:regionArea>
<placeName><settlement type="city">Tianjin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yu, Gang" sort="Yu, Gang" uniqKey="Yu G" first="Gang" last="Yu">Gang Yu</name>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Nanlou Respiratory Department, Chinese PLA General Hospital, Beijing 100853</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
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<affiliation wicri:level="1"><nlm:affiliation>Department of Respiratory Medicine, The Second affiliated hospital of Nanchang University, Nanchang, Jiangxi 33000, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Respiratory Medicine, The Second affiliated hospital of Nanchang University, Nanchang, Jiangxi 33000</wicri:regionArea>
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<author><name sortKey="Yu, Juan" sort="Yu, Juan" uniqKey="Yu J" first="Juan" last="Yu">Juan Yu</name>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medical Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
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<author><name sortKey="Han, Ling" sort="Han, Ling" uniqKey="Han L" first="Ling" last="Han">Ling Han</name>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020</wicri:regionArea>
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<author><name sortKey="Xue, Ting" sort="Xue, Ting" uniqKey="Xue T" first="Ting" last="Xue">Ting Xue</name>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medical Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
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<author><name sortKey="Sun, Zhina" sort="Sun, Zhina" uniqKey="Sun Z" first="Zhina" last="Sun">Zhina Sun</name>
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<author><name sortKey="Chen, Song" sort="Chen, Song" uniqKey="Chen S" first="Song" last="Chen">Song Chen</name>
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<country xml:lang="fr">République populaire de Chine</country>
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</placeName>
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<author><name sortKey="Fang, Chunming" sort="Fang, Chunming" uniqKey="Fang C" first="Chunming" last="Fang">Chunming Fang</name>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020</wicri:regionArea>
<placeName><settlement type="city">Tianjin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zhao, Chunxiao" sort="Zhao, Chunxiao" uniqKey="Zhao C" first="Chunxiao" last="Zhao">Chunxiao Zhao</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020</wicri:regionArea>
<placeName><settlement type="city">Tianjin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Niu, Qing" sort="Niu, Qing" uniqKey="Niu Q" first="Qing" last="Niu">Qing Niu</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020</wicri:regionArea>
<placeName><settlement type="city">Tianjin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yang, Fei" sort="Yang, Fei" uniqKey="Yang F" first="Fei" last="Yang">Fei Yang</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020</wicri:regionArea>
<placeName><settlement type="city">Tianjin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Han, Zhongchao" sort="Han, Zhongchao" uniqKey="Han Z" first="Zhongchao" last="Han">Zhongchao Han</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020</wicri:regionArea>
<placeName><settlement type="city">Tianjin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cheng, Tao" sort="Cheng, Tao" uniqKey="Cheng T" first="Tao" last="Cheng">Tao Cheng</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020</wicri:regionArea>
<placeName><settlement type="city">Tianjin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zeng, Yun" sort="Zeng, Yun" uniqKey="Zeng Y" first="Yun" last="Zeng">Yun Zeng</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Hematology, First Affiliated Hosptial of Kunming Medical University, Kunming 650032, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Hematology, First Affiliated Hosptial of Kunming Medical University, Kunming 650032</wicri:regionArea>
<wicri:noRegion>Kunming 650032</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Liao, Fang" sort="Liao, Fang" uniqKey="Liao F" first="Fang" last="Liao">Fang Liao</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Medical Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medical Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Xu, Guogang" sort="Xu, Guogang" uniqKey="Xu G" first="Guogang" last="Xu">Guogang Xu</name>
<affiliation wicri:level="1"><nlm:affiliation>Nanlou Respiratory Department, Chinese PLA General Hospital, Beijing 100853, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Nanlou Respiratory Department, Chinese PLA General Hospital, Beijing 100853</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Department of Respiratory Medicine, The Second affiliated hospital of Nanchang University, Nanchang, Jiangxi 33000, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Respiratory Medicine, The Second affiliated hospital of Nanchang University, Nanchang, Jiangxi 33000</wicri:regionArea>
<wicri:noRegion>Jiangxi 33000</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Feng, Xiaoming" sort="Feng, Xiaoming" uniqKey="Feng X" first="Xiaoming" last="Feng">Xiaoming Feng</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020</wicri:regionArea>
<placeName><settlement type="city">Tianjin</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Cell death & disease</title>
<idno type="eISSN">2041-4889</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>Cell Differentiation (genetics)</term>
<term>Dendritic Cells (immunology)</term>
<term>Dendritic Cells (metabolism)</term>
<term>Dendritic Cells (pathology)</term>
<term>Homeostasis (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Lymphoproliferative Disorders (genetics)</term>
<term>Lymphoproliferative Disorders (immunology)</term>
<term>Lymphoproliferative Disorders (pathology)</term>
<term>Mechanistic Target of Rapamycin Complex 1 (MeSH)</term>
<term>Mice (MeSH)</term>
<term>Multiprotein Complexes (genetics)</term>
<term>Signal Transduction (genetics)</term>
<term>T-Lymphocytes (immunology)</term>
<term>T-Lymphocytes (metabolism)</term>
<term>T-Lymphocytes (pathology)</term>
<term>TOR Serine-Threonine Kinases (biosynthesis)</term>
<term>TOR Serine-Threonine Kinases (genetics)</term>
<term>Tuberous Sclerosis Complex 1 Protein (MeSH)</term>
<term>Tumor Suppressor Proteins (biosynthesis)</term>
<term>Tumor Suppressor Proteins (genetics)</term>
<term>Tumor Suppressor Proteins (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term>
<term>Cellules dendritiques (anatomopathologie)</term>
<term>Cellules dendritiques (immunologie)</term>
<term>Cellules dendritiques (métabolisme)</term>
<term>Complexe-1 cible mécanistique de la rapamycine (MeSH)</term>
<term>Complexes multiprotéiques (génétique)</term>
<term>Différenciation cellulaire (génétique)</term>
<term>Homéostasie (MeSH)</term>
<term>Humains (MeSH)</term>
<term>Lymphocytes T (anatomopathologie)</term>
<term>Lymphocytes T (immunologie)</term>
<term>Lymphocytes T (métabolisme)</term>
<term>Protéine-1 du complexe de la sclérose tubéreuse (MeSH)</term>
<term>Protéines suppresseurs de tumeurs (biosynthèse)</term>
<term>Protéines suppresseurs de tumeurs (génétique)</term>
<term>Protéines suppresseurs de tumeurs (immunologie)</term>
<term>Souris (MeSH)</term>
<term>Syndromes lymphoprolifératifs (anatomopathologie)</term>
<term>Syndromes lymphoprolifératifs (génétique)</term>
<term>Syndromes lymphoprolifératifs (immunologie)</term>
<term>Sérine-thréonine kinases TOR (biosynthèse)</term>
<term>Sérine-thréonine kinases TOR (génétique)</term>
<term>Transduction du signal (génétique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>TOR Serine-Threonine Kinases</term>
<term>Tumor Suppressor Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Multiprotein Complexes</term>
<term>TOR Serine-Threonine Kinases</term>
<term>Tumor Suppressor Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Tumor Suppressor Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en"><term>Mechanistic Target of Rapamycin Complex 1</term>
<term>Tuberous Sclerosis Complex 1 Protein</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Cellules dendritiques</term>
<term>Lymphocytes T</term>
<term>Syndromes lymphoprolifératifs</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Protéines suppresseurs de tumeurs</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Cell Differentiation</term>
<term>Lymphoproliferative Disorders</term>
<term>Signal Transduction</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Complexes multiprotéiques</term>
<term>Différenciation cellulaire</term>
<term>Protéines suppresseurs de tumeurs</term>
<term>Syndromes lymphoprolifératifs</term>
<term>Sérine-thréonine kinases TOR</term>
<term>Transduction du signal</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Cellules dendritiques</term>
<term>Lymphocytes T</term>
<term>Protéines suppresseurs de tumeurs</term>
<term>Syndromes lymphoprolifératifs</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Dendritic Cells</term>
<term>Lymphoproliferative Disorders</term>
<term>T-Lymphocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Dendritic Cells</term>
<term>T-Lymphocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cellules dendritiques</term>
<term>Lymphocytes T</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Dendritic Cells</term>
<term>Lymphoproliferative Disorders</term>
<term>T-Lymphocytes</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Homeostasis</term>
<term>Humans</term>
<term>Mice</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Complexe-1 cible mécanistique de la rapamycine</term>
<term>Homéostasie</term>
<term>Humains</term>
<term>Protéine-1 du complexe de la sclérose tubéreuse</term>
<term>Souris</term>
</keywords>
</textClass>
</profileDesc>
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<front><div type="abstract" xml:lang="en">Dendritic cells (DCs) are pivotal to the induction of adaptive T-cell immune responses. Recent evidence highlights a critical role of tuberous sclerosis complex 1 (Tsc1), a primarily upstream negative regulator of mammalian target of rapamycin (mTOR), in DC development, but whether and how Tsc1 directly regulate mature DC function in vivo remains elusive. Here we show that selective disruption of Tsc1 in DCs results in a lymphoproliferative disorder with the spontaneous activation of T cells. Tsc1 deficiency results in the activation of mTORC1-PPARγ pathway, which leads to the upregulation of neuropilin-1 (Nrp1) expression on DCs to stimulate naive T-cell proliferation. However, Tsc1-deficient DCs have defects in the ability to induce antigen-specific T-cell responses in vitro and in vivo owing to impaired survival during antigen transportation and presentation. Indeed, Tsc1 promotes DC survival through restraining independent mTORC1 and ROS-Bim pathways. Our study identifies Tsc1 as a crucial signaling checkpoint in DCs essential for preserving T-cell homeostasis and response.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28079897</PMID>
<DateCompleted><Year>2017</Year>
<Month>10</Month>
<Day>26</Day>
</DateCompleted>
<DateRevised><Year>2018</Year>
<Month>12</Month>
<Day>02</Day>
</DateRevised>
<Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2041-4889</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>8</Volume>
<Issue>1</Issue>
<PubDate><Year>2017</Year>
<Month>01</Month>
<Day>12</Day>
</PubDate>
</JournalIssue>
<Title>Cell death & disease</Title>
<ISOAbbreviation>Cell Death Dis</ISOAbbreviation>
</Journal>
<ArticleTitle>Tsc1 expression by dendritic cells is required to preserve T-cell homeostasis and response.</ArticleTitle>
<Pagination><MedlinePgn>e2553</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1038/cddis.2016.487</ELocationID>
<Abstract><AbstractText>Dendritic cells (DCs) are pivotal to the induction of adaptive T-cell immune responses. Recent evidence highlights a critical role of tuberous sclerosis complex 1 (Tsc1), a primarily upstream negative regulator of mammalian target of rapamycin (mTOR), in DC development, but whether and how Tsc1 directly regulate mature DC function in vivo remains elusive. Here we show that selective disruption of Tsc1 in DCs results in a lymphoproliferative disorder with the spontaneous activation of T cells. Tsc1 deficiency results in the activation of mTORC1-PPARγ pathway, which leads to the upregulation of neuropilin-1 (Nrp1) expression on DCs to stimulate naive T-cell proliferation. However, Tsc1-deficient DCs have defects in the ability to induce antigen-specific T-cell responses in vitro and in vivo owing to impaired survival during antigen transportation and presentation. Indeed, Tsc1 promotes DC survival through restraining independent mTORC1 and ROS-Bim pathways. Our study identifies Tsc1 as a crucial signaling checkpoint in DCs essential for preserving T-cell homeostasis and response.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Luo</LastName>
<ForeName>Yuechen</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Li</LastName>
<ForeName>Wenwen</ForeName>
<Initials>W</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yu</LastName>
<ForeName>Gang</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Nanlou Respiratory Department, Chinese PLA General Hospital, Beijing 100853, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Respiratory Medicine, The Second affiliated hospital of Nanchang University, Nanchang, Jiangxi 33000, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yu</LastName>
<ForeName>Juan</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Medical Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Han</LastName>
<ForeName>Ling</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Xue</LastName>
<ForeName>Ting</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Department of Medical Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sun</LastName>
<ForeName>Zhina</ForeName>
<Initials>Z</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chen</LastName>
<ForeName>Song</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Fang</LastName>
<ForeName>Chunming</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhao</LastName>
<ForeName>Chunxiao</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Niu</LastName>
<ForeName>Qing</ForeName>
<Initials>Q</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yang</LastName>
<ForeName>Fei</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Han</LastName>
<ForeName>Zhongchao</ForeName>
<Initials>Z</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cheng</LastName>
<ForeName>Tao</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zeng</LastName>
<ForeName>Yun</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Department of Hematology, First Affiliated Hosptial of Kunming Medical University, Kunming 650032, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Liao</LastName>
<ForeName>Fang</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Department of Medical Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Xu</LastName>
<ForeName>Guogang</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Nanlou Respiratory Department, Chinese PLA General Hospital, Beijing 100853, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Respiratory Medicine, The Second affiliated hospital of Nanchang University, Nanchang, Jiangxi 33000, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Feng</LastName>
<ForeName>Xiaoming</ForeName>
<Initials>X</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2017</Year>
<Month>01</Month>
<Day>12</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>England</Country>
<MedlineTA>Cell Death Dis</MedlineTA>
<NlmUniqueID>101524092</NlmUniqueID>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D046912">Multiprotein Complexes</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C000624650">TSC1 protein, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C000624651">Tsc1 protein, mouse</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000077004">Tuberous Sclerosis Complex 1 Protein</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D025521">Tumor Suppressor Proteins</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>
<Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber>
<NameOfSubstance UI="D000076222">Mechanistic Target of Rapamycin Complex 1</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002454" MajorTopicYN="N">Cell Differentiation</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D003713" MajorTopicYN="N">Dendritic Cells</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006706" MajorTopicYN="N">Homeostasis</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008232" MajorTopicYN="N">Lymphoproliferative Disorders</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000076222" MajorTopicYN="N">Mechanistic Target of Rapamycin Complex 1</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D046912" MajorTopicYN="N">Multiprotein Complexes</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013601" MajorTopicYN="N">T-Lymphocytes</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName>
<QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000077004" MajorTopicYN="N">Tuberous Sclerosis Complex 1 Protein</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D025521" MajorTopicYN="N">Tumor Suppressor Proteins</DescriptorName>
<QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
</MeshHeadingList>
</MedlineCitation>
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<PubMedPubDate PubStatus="revised"><Year>2016</Year>
<Month>12</Month>
<Day>12</Day>
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<PubMedPubDate PubStatus="accepted"><Year>2016</Year>
<Month>12</Month>
<Day>13</Day>
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<ArticleId IdType="doi">10.1038/cddis.2016.487</ArticleId>
<ArticleId IdType="pmc">PMC5386387</ArticleId>
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	Serveur d'exploration sur la rapamycine et les champignons
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Tsc1 expression by dendritic cells is required to preserve T-cell homeostasis and response.

Tsc1 expression by dendritic cells is required to preserve T-cell homeostasis and response.

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