RapamycinFungusV1, Main, Exploration, bibRecord, 000252

Reciprocal regulation of STING and TCR signaling by mTORC1 for T-cell activation and function.

Identifieur interne : 000252 ( Main/Exploration ); précédent : 000251; suivant : 000253

Reciprocal regulation of STING and TCR signaling by mTORC1 for T-cell activation and function.

Auteurs : Takayuki Imanishi [Japon] ; Midori Unno [Japon] ; Wakana Kobayashi [Japon] ; Natsumi Yoneda [Japon] ; Satoshi Matsuda [Japon] ; Kazutaka Ikeda [Japon] ; Takayuki Hoshii [Japon] ; Atsushi Hirao [Japon] ; Kensuke Miyake [Japon] ; Glen N. Barber [États-Unis] ; Makoto Arita [Japon] ; Ken J. Ishii [Japon] ; Shizuo Akira [Japon] ; Takashi Saito [Japon]

Source :

Life science alliance [ 2575-1077 ] ; 2019.

RBID : pubmed:30683688

Descripteurs français

English descriptors

KwdEn :
- Animals (MeSH), CD4-Positive T-Lymphocytes (metabolism), CD8-Positive T-Lymphocytes (metabolism), Cell Cycle Checkpoints (genetics), Cell Line, Tumor (MeSH), Cell Proliferation (MeSH), Heterografts (MeSH), Interferon Regulatory Factor-3 (metabolism), Interferon Regulatory Factor-7 (metabolism), Interferon Type I (metabolism), Lymphocyte Activation (immunology), Mechanistic Target of Rapamycin Complex 1 (metabolism), Membrane Proteins (genetics), Membrane Proteins (metabolism), Mice (MeSH), Mice, Inbred C57BL (MeSH), Mice, Knockout (MeSH), Nucleotides, Cyclic (metabolism), Receptors, Antigen, T-Cell (metabolism), Tumor Burden (MeSH).
MESH :
- chemical , genetics : Membrane Proteins.
- chemical , metabolism : Interferon Regulatory Factor-3, Interferon Regulatory Factor-7, Interferon Type I, Mechanistic Target of Rapamycin Complex 1, Membrane Proteins, Nucleotides, Cyclic, Receptors, Antigen, T-Cell.
- genetics : Cell Cycle Checkpoints.
- immunology : Lymphocyte Activation.
- metabolism : CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes.
- Animals, Cell Line, Tumor, Cell Proliferation, Heterografts, Mice, Mice, Inbred C57BL, Mice, Knockout, Tumor Burden.

Abstract

Stimulator of interferon genes (STING) plays a key role in detecting cytosolic DNA and induces type I interferon (IFN-I) responses for host defense against pathogens. Although T cells highly express STING, its physiological role remains unknown. Here, we show that costimulation of T cells with the STING ligand cGAMP and TCR leads to IFN-I production and strongly inhibits T-cell growth. TCR-mediated mTORC1 activation and sustained activation of IRF3 are required for cGAMP-induced IFN-I production, and the mTORC1 activity is partially counteracted by cGAMP, thereby blocking proliferation. This mTORC1 inhibition in response to costimulation depends on IRF3 and IRF7. Effector T cells produce much higher IFN-I levels than innate cells in response to cGAMP. Finally, we demonstrated that STING stimulation in T cells is effective in inducing antitumor responses in vivo. Our studies demonstrate that the outputs of STING and TCR signaling pathways are mutually regulated through mTORC1 to modulate T-cell functions.

DOI: 10.26508/lsa.201800282
PubMed: 30683688
PubMed Central: PMC6348487

Affiliations:

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

to stream Main, to step Corpus: 000361
to stream Main, to step Curation: 000361

Le document en format XML

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<author><name sortKey="Miyake, Kensuke" sort="Miyake, Kensuke" uniqKey="Miyake K" first="Kensuke" last="Miyake">Kensuke Miyake</name>
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<author><name sortKey="Arita, Makoto" sort="Arita, Makoto" uniqKey="Arita M" first="Makoto" last="Arita">Makoto Arita</name>
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<wicri:regionArea>Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo</wicri:regionArea>
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<author><name sortKey="Ishii, Ken J" sort="Ishii, Ken J" uniqKey="Ishii K" first="Ken J" last="Ishii">Ken J. Ishii</name>
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<author><name sortKey="Akira, Shizuo" sort="Akira, Shizuo" uniqKey="Akira S" first="Shizuo" last="Akira">Shizuo Akira</name>
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<country xml:lang="fr">Japon</country>
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<wicri:noRegion>Osaka</wicri:noRegion>
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<author><name sortKey="Saito, Takashi" sort="Saito, Takashi" uniqKey="Saito T" first="Takashi" last="Saito">Takashi Saito</name>
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<country wicri:rule="url">Japon</country>
<wicri:regionArea>Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama</wicri:regionArea>
<wicri:noRegion>Yokohama</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory for Cell Signaling, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Laboratory for Cell Signaling, WPI Immunology Frontier Research Center, Osaka University, Osaka</wicri:regionArea>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Reciprocal regulation of STING and TCR signaling by mTORC1 for T-cell activation and function.</title>
<author><name sortKey="Imanishi, Takayuki" sort="Imanishi, Takayuki" uniqKey="Imanishi T" first="Takayuki" last="Imanishi">Takayuki Imanishi</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan takayuki.imanishi@riken.jp.</nlm:affiliation>
<country wicri:rule="url">Japon</country>
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<author><name sortKey="Unno, Midori" sort="Unno, Midori" uniqKey="Unno M" first="Midori" last="Unno">Midori Unno</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama</wicri:regionArea>
<wicri:noRegion>Yokohama</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kobayashi, Wakana" sort="Kobayashi, Wakana" uniqKey="Kobayashi W" first="Wakana" last="Kobayashi">Wakana Kobayashi</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama</wicri:regionArea>
<wicri:noRegion>Yokohama</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Yoneda, Natsumi" sort="Yoneda, Natsumi" uniqKey="Yoneda N" first="Natsumi" last="Yoneda">Natsumi Yoneda</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama</wicri:regionArea>
<wicri:noRegion>Yokohama</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Matsuda, Satoshi" sort="Matsuda, Satoshi" uniqKey="Matsuda S" first="Satoshi" last="Matsuda">Satoshi Matsuda</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Cell Signaling, Institute of Biomedical Sciences, Kansai Medical University, Hirakata, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Cell Signaling, Institute of Biomedical Sciences, Kansai Medical University, Hirakata</wicri:regionArea>
<wicri:noRegion>Hirakata</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ikeda, Kazutaka" sort="Ikeda, Kazutaka" uniqKey="Ikeda K" first="Kazutaka" last="Ikeda">Kazutaka Ikeda</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Yokohama</wicri:regionArea>
<wicri:noRegion>Yokohama</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Japan Agency for Medical Research and Development (AMED)-PRIME, Japan Agency for Medical Research and Development, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Japan Agency for Medical Research and Development (AMED)-PRIME, Japan Agency for Medical Research and Development, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Graduate School of Medical Life Science, Yokohama City University, Yokohama</wicri:regionArea>
<wicri:noRegion>Yokohama</wicri:noRegion>
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</author>
<author><name sortKey="Hoshii, Takayuki" sort="Hoshii, Takayuki" uniqKey="Hoshii T" first="Takayuki" last="Hoshii">Takayuki Hoshii</name>
<affiliation wicri:level="1"><nlm:affiliation>Division of Molecular Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Division of Molecular Genetics, Cancer Research Institute, Kanazawa University, Kanazawa</wicri:regionArea>
<wicri:noRegion>Kanazawa</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hirao, Atsushi" sort="Hirao, Atsushi" uniqKey="Hirao A" first="Atsushi" last="Hirao">Atsushi Hirao</name>
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<country xml:lang="fr">Japon</country>
<wicri:regionArea>Division of Molecular Genetics, Cancer Research Institute, Kanazawa University, Kanazawa</wicri:regionArea>
<wicri:noRegion>Kanazawa</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Miyake, Kensuke" sort="Miyake, Kensuke" uniqKey="Miyake K" first="Kensuke" last="Miyake">Kensuke Miyake</name>
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<country xml:lang="fr">Japon</country>
<wicri:regionArea>Division of Innate Immunity, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
<orgName type="university">Université de Tokyo</orgName>
</affiliation>
</author>
<author><name sortKey="Barber, Glen N" sort="Barber, Glen N" uniqKey="Barber G" first="Glen N" last="Barber">Glen N. Barber</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Cell Biology and the Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Cell Biology and the Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL</wicri:regionArea>
<placeName><region type="state">Floride</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Arita, Makoto" sort="Arita, Makoto" uniqKey="Arita M" first="Makoto" last="Arita">Makoto Arita</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Yokohama</wicri:regionArea>
<wicri:noRegion>Yokohama</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Graduate School of Medical Life Science, Yokohama City University, Yokohama</wicri:regionArea>
<wicri:noRegion>Yokohama</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ishii, Ken J" sort="Ishii, Ken J" uniqKey="Ishii K" first="Ken J" last="Ishii">Ken J. Ishii</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory of Vaccine Science, World Premier International Research Center Initiative (WPI) Immunology Frontier Research Center, Osaka University, Suita, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Laboratory of Vaccine Science, World Premier International Research Center Initiative (WPI) Immunology Frontier Research Center, Osaka University, Suita</wicri:regionArea>
<wicri:noRegion>Suita</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka</wicri:regionArea>
<wicri:noRegion>Osaka</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Akira, Shizuo" sort="Akira, Shizuo" uniqKey="Akira S" first="Shizuo" last="Akira">Shizuo Akira</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka</wicri:regionArea>
<wicri:noRegion>Osaka</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Saito, Takashi" sort="Saito, Takashi" uniqKey="Saito T" first="Takashi" last="Saito">Takashi Saito</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan takashi.saito@riken.jp.</nlm:affiliation>
<country wicri:rule="url">Japon</country>
<wicri:regionArea>Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama</wicri:regionArea>
<wicri:noRegion>Yokohama</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory for Cell Signaling, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Laboratory for Cell Signaling, WPI Immunology Frontier Research Center, Osaka University, Osaka</wicri:regionArea>
<wicri:noRegion>Osaka</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Life science alliance</title>
<idno type="eISSN">2575-1077</idno>
<imprint><date when="2019" type="published">2019</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term>
<term>CD4-Positive T-Lymphocytes (metabolism)</term>
<term>CD8-Positive T-Lymphocytes (metabolism)</term>
<term>Cell Cycle Checkpoints (genetics)</term>
<term>Cell Line, Tumor (MeSH)</term>
<term>Cell Proliferation (MeSH)</term>
<term>Heterografts (MeSH)</term>
<term>Interferon Regulatory Factor-3 (metabolism)</term>
<term>Interferon Regulatory Factor-7 (metabolism)</term>
<term>Interferon Type I (metabolism)</term>
<term>Lymphocyte Activation (immunology)</term>
<term>Mechanistic Target of Rapamycin Complex 1 (metabolism)</term>
<term>Membrane Proteins (genetics)</term>
<term>Membrane Proteins (metabolism)</term>
<term>Mice (MeSH)</term>
<term>Mice, Inbred C57BL (MeSH)</term>
<term>Mice, Knockout (MeSH)</term>
<term>Nucleotides, Cyclic (metabolism)</term>
<term>Receptors, Antigen, T-Cell (metabolism)</term>
<term>Tumor Burden (MeSH)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Activation des lymphocytes (immunologie)</term>
<term>Animaux (MeSH)</term>
<term>Charge tumorale (MeSH)</term>
<term>Complexe-1 cible mécanistique de la rapamycine (métabolisme)</term>
<term>Facteur-3 de régulation d'interféron (métabolisme)</term>
<term>Facteur-7 de régulation d'interféron (métabolisme)</term>
<term>Hétérogreffes (MeSH)</term>
<term>Interféron de type I (métabolisme)</term>
<term>Lignée cellulaire tumorale (MeSH)</term>
<term>Lymphocytes T CD4+ (métabolisme)</term>
<term>Lymphocytes T CD8+ (métabolisme)</term>
<term>Nucléotides cycliques (métabolisme)</term>
<term>Points de contrôle du cycle cellulaire (génétique)</term>
<term>Prolifération cellulaire (MeSH)</term>
<term>Protéines membranaires (génétique)</term>
<term>Protéines membranaires (métabolisme)</term>
<term>Récepteurs aux antigènes des cellules T (métabolisme)</term>
<term>Souris (MeSH)</term>
<term>Souris de lignée C57BL (MeSH)</term>
<term>Souris knockout (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Membrane Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Interferon Regulatory Factor-3</term>
<term>Interferon Regulatory Factor-7</term>
<term>Interferon Type I</term>
<term>Mechanistic Target of Rapamycin Complex 1</term>
<term>Membrane Proteins</term>
<term>Nucleotides, Cyclic</term>
<term>Receptors, Antigen, T-Cell</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Cell Cycle Checkpoints</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Points de contrôle du cycle cellulaire</term>
<term>Protéines membranaires</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Activation des lymphocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Lymphocyte Activation</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term>
<term>CD8-Positive T-Lymphocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Complexe-1 cible mécanistique de la rapamycine</term>
<term>Facteur-3 de régulation d'interféron</term>
<term>Facteur-7 de régulation d'interféron</term>
<term>Interféron de type I</term>
<term>Lymphocytes T CD4+</term>
<term>Lymphocytes T CD8+</term>
<term>Nucléotides cycliques</term>
<term>Protéines membranaires</term>
<term>Récepteurs aux antigènes des cellules T</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Cell Line, Tumor</term>
<term>Cell Proliferation</term>
<term>Heterografts</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Knockout</term>
<term>Tumor Burden</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Charge tumorale</term>
<term>Hétérogreffes</term>
<term>Lignée cellulaire tumorale</term>
<term>Prolifération cellulaire</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Souris knockout</term>
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<front><div type="abstract" xml:lang="en">Stimulator of interferon genes (STING) plays a key role in detecting cytosolic DNA and induces type I interferon (IFN-I) responses for host defense against pathogens. Although T cells highly express STING, its physiological role remains unknown. Here, we show that costimulation of T cells with the STING ligand cGAMP and TCR leads to IFN-I production and strongly inhibits T-cell growth. TCR-mediated mTORC1 activation and sustained activation of IRF3 are required for cGAMP-induced IFN-I production, and the mTORC1 activity is partially counteracted by cGAMP, thereby blocking proliferation. This mTORC1 inhibition in response to costimulation depends on IRF3 and IRF7. Effector T cells produce much higher IFN-I levels than innate cells in response to cGAMP. Finally, we demonstrated that STING stimulation in T cells is effective in inducing antitumor responses in vivo. Our studies demonstrate that the outputs of STING and TCR signaling pathways are mutually regulated through mTORC1 to modulate T-cell functions.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30683688</PMID>
<DateCompleted><Year>2020</Year>
<Month>02</Month>
<Day>26</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>03</Month>
<Day>09</Day>
</DateRevised>
<Article PubModel="Electronic-Print"><Journal><ISSN IssnType="Electronic">2575-1077</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>2</Volume>
<Issue>1</Issue>
<PubDate><Year>2019</Year>
<Month>02</Month>
</PubDate>
</JournalIssue>
<Title>Life science alliance</Title>
<ISOAbbreviation>Life Sci Alliance</ISOAbbreviation>
</Journal>
<ArticleTitle>Reciprocal regulation of STING and TCR signaling by mTORC1 for T-cell activation and function.</ArticleTitle>
<ELocationID EIdType="pii" ValidYN="Y">e201800282</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.26508/lsa.201800282</ELocationID>
<Abstract><AbstractText>Stimulator of interferon genes (STING) plays a key role in detecting cytosolic DNA and induces type I interferon (IFN-I) responses for host defense against pathogens. Although T cells highly express STING, its physiological role remains unknown. Here, we show that costimulation of T cells with the STING ligand cGAMP and TCR leads to IFN-I production and strongly inhibits T-cell growth. TCR-mediated mTORC1 activation and sustained activation of IRF3 are required for cGAMP-induced IFN-I production, and the mTORC1 activity is partially counteracted by cGAMP, thereby blocking proliferation. This mTORC1 inhibition in response to costimulation depends on IRF3 and IRF7. Effector T cells produce much higher IFN-I levels than innate cells in response to cGAMP. Finally, we demonstrated that STING stimulation in T cells is effective in inducing antitumor responses in vivo. Our studies demonstrate that the outputs of STING and TCR signaling pathways are mutually regulated through mTORC1 to modulate T-cell functions.</AbstractText>
<CopyrightInformation>© 2019 Imanishi et al.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Imanishi</LastName>
<ForeName>Takayuki</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan takayuki.imanishi@riken.jp.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Unno</LastName>
<ForeName>Midori</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kobayashi</LastName>
<ForeName>Wakana</ForeName>
<Initials>W</Initials>
<AffiliationInfo><Affiliation>Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yoneda</LastName>
<ForeName>Natsumi</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Matsuda</LastName>
<ForeName>Satoshi</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Cell Signaling, Institute of Biomedical Sciences, Kansai Medical University, Hirakata, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ikeda</LastName>
<ForeName>Kazutaka</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Japan Agency for Medical Research and Development (AMED)-PRIME, Japan Agency for Medical Research and Development, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hoshii</LastName>
<ForeName>Takayuki</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Division of Molecular Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hirao</LastName>
<ForeName>Atsushi</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Division of Molecular Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Miyake</LastName>
<ForeName>Kensuke</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Barber</LastName>
<ForeName>Glen N</ForeName>
<Initials>GN</Initials>
<AffiliationInfo><Affiliation>Department of Cell Biology and the Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Arita</LastName>
<ForeName>Makoto</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ishii</LastName>
<ForeName>Ken J</ForeName>
<Initials>KJ</Initials>
<AffiliationInfo><Affiliation>Laboratory of Vaccine Science, World Premier International Research Center Initiative (WPI) Immunology Frontier Research Center, Osaka University, Suita, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Akira</LastName>
<ForeName>Shizuo</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Saito</LastName>
<ForeName>Takashi</ForeName>
<Initials>T</Initials>
<Identifier Source="ORCID">0000-0001-9495-3547</Identifier>
<AffiliationInfo><Affiliation>Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan takashi.saito@riken.jp.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Laboratory for Cell Signaling, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>R01 CA194404</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2019</Year>
<Month>01</Month>
<Day>25</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Life Sci Alliance</MedlineTA>
<NlmUniqueID>101728869</NlmUniqueID>
<ISSNLinking>2575-1077</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D050838">Interferon Regulatory Factor-3</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D050839">Interferon Regulatory Factor-7</NameOfSubstance>
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<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D007370">Interferon Type I</NameOfSubstance>
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<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C494233">Irf3 protein, mouse</NameOfSubstance>
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<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C494235">Irf7 protein, mouse</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C530855">MPYS protein, mouse</NameOfSubstance>
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<NameOfSubstance UI="D008565">Membrane Proteins</NameOfSubstance>
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<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D009712">Nucleotides, Cyclic</NameOfSubstance>
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<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D011948">Receptors, Antigen, T-Cell</NameOfSubstance>
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<MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015496" MajorTopicYN="N">CD4-Positive T-Lymphocytes</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018414" MajorTopicYN="N">CD8-Positive T-Lymphocytes</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D059447" MajorTopicYN="N">Cell Cycle Checkpoints</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D064593" MajorTopicYN="N">Heterografts</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D050838" MajorTopicYN="N">Interferon Regulatory Factor-3</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D050839" MajorTopicYN="N">Interferon Regulatory Factor-7</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007370" MajorTopicYN="N">Interferon Type I</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008213" MajorTopicYN="N">Lymphocyte Activation</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000076222" MajorTopicYN="N">Mechanistic Target of Rapamycin Complex 1</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008565" MajorTopicYN="N">Membrane Proteins</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</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="D018345" MajorTopicYN="N">Mice, Knockout</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009712" MajorTopicYN="N">Nucleotides, Cyclic</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011948" MajorTopicYN="N">Receptors, Antigen, T-Cell</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D047368" MajorTopicYN="N">Tumor Burden</DescriptorName>
</MeshHeading>
</MeshHeadingList>
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<Month>12</Month>
<Day>26</Day>
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<PubMedPubDate PubStatus="accepted"><Year>2019</Year>
<Month>01</Month>
<Day>07</Day>
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<tree><country name="Japon"><noRegion><name sortKey="Imanishi, Takayuki" sort="Imanishi, Takayuki" uniqKey="Imanishi T" first="Takayuki" last="Imanishi">Takayuki Imanishi</name>
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	Serveur d'exploration sur la rapamycine et les champignons
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Reciprocal regulation of STING and TCR signaling by mTORC1 for T-cell activation and function.

Reciprocal regulation of STING and TCR signaling by mTORC1 for T-cell activation and function.

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