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c-Maf-dependent Treg cell control of intestinal TH17 cells and IgA establishes host-microbiota homeostasis.

Identifieur interne : 000177 ( Main/Exploration ); précédent : 000176; suivant : 000178

c-Maf-dependent Treg cell control of intestinal TH17 cells and IgA establishes host-microbiota homeostasis.

Auteurs : Christian Neumann [Allemagne] ; Jonas Blume [Australie] ; Urmi Roy [Allemagne] ; Peggy P. Teh [Australie] ; Ajithkumar Vasanthakumar [Australie] ; Alexander Beller [Allemagne] ; Yang Liao [Australie] ; Frederik Heinrich [Allemagne] ; Teresita L. Arenzana [États-Unis] ; Jason A. Hackney [États-Unis] ; Celine Eidenschenk [États-Unis] ; Eric J C. Gálvez [Allemagne] ; Christina Stehle [Allemagne] ; Gitta A. Heinz [Allemagne] ; Patrick Maschmeyer [Allemagne] ; Tom Sidwell [Australie] ; Yifang Hu [Australie] ; Derk Amsen [Pays-Bas] ; Chiara Romagnani [Allemagne] ; Hyun-Dong Chang [Allemagne] ; Andrey Kruglov [Allemagne, Russie] ; Mir-Farzin Mashreghi [Allemagne] ; Wei Shi [Australie] ; Till Strowig [Allemagne] ; Sascha Rutz [États-Unis] ; Axel Kallies [Australie] ; Alexander Scheffold [Allemagne]

Source :

RBID : pubmed:30778241

Descripteurs français

English descriptors

Abstract

Foxp3+ regulatory T cells (Treg cells) are crucial for the maintenance of immune homeostasis both in lymphoid tissues and in non-lymphoid tissues. Here we demonstrate that the ability of intestinal Treg cells to constrain microbiota-dependent interleukin (IL)-17-producing helper T cell (TH17 cell) and immunoglobulin A responses critically required expression of the transcription factor c-Maf. The terminal differentiation and function of several intestinal Treg cell populations, including RORγt+ Treg cells and follicular regulatory T cells, were c-Maf dependent. c-Maf controlled Treg cell-derived IL-10 production and prevented excessive signaling via the kinases PI(3)K (phosphatidylinositol-3-OH kinase) and Akt and the metabolic checkpoint kinase complex mTORC1 (mammalian target of rapamycin) and expression of inflammatory cytokines in intestinal Treg cells. c-Maf deficiency in Treg cells led to profound dysbiosis of the intestinal microbiota, which when transferred to germ-free mice was sufficient to induce exacerbated intestinal TH17 responses, even in a c-Maf-competent environment. Thus, c-Maf acts to preserve the identity and function of intestinal Treg cells, which is essential for the establishment of host-microbe symbiosis.

DOI: 10.1038/s41590-019-0316-2
PubMed: 30778241


Affiliations:


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Le document en format XML

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<name sortKey="Vasanthakumar, Ajithkumar" sort="Vasanthakumar, Ajithkumar" uniqKey="Vasanthakumar A" first="Ajithkumar" last="Vasanthakumar">Ajithkumar Vasanthakumar</name>
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<name sortKey="Beller, Alexander" sort="Beller, Alexander" uniqKey="Beller A" first="Alexander" last="Beller">Alexander Beller</name>
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<name sortKey="Liao, Yang" sort="Liao, Yang" uniqKey="Liao Y" first="Yang" last="Liao">Yang Liao</name>
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<nlm:affiliation>Department of Medical Biology, University of Melbourne, Melbourne, Australia.</nlm:affiliation>
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<wicri:regionArea>Department of Medical Biology, University of Melbourne, Melbourne</wicri:regionArea>
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<settlement type="city">Melbourne</settlement>
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<name sortKey="Arenzana, Teresita L" sort="Arenzana, Teresita L" uniqKey="Arenzana T" first="Teresita L" last="Arenzana">Teresita L. Arenzana</name>
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<nlm:affiliation>Department of Cancer Immunology, Genentech, San Francisco, CA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Cancer Immunology, Genentech, San Francisco, CA</wicri:regionArea>
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<name sortKey="Hackney, Jason A" sort="Hackney, Jason A" uniqKey="Hackney J" first="Jason A" last="Hackney">Jason A. Hackney</name>
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<nlm:affiliation>Department of Bioinformatics and Computational Biology, Genentech, San Francisco, CA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Bioinformatics and Computational Biology, Genentech, San Francisco, CA</wicri:regionArea>
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<region type="state">Californie</region>
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<name sortKey="Eidenschenk, Celine" sort="Eidenschenk, Celine" uniqKey="Eidenschenk C" first="Celine" last="Eidenschenk">Celine Eidenschenk</name>
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<nlm:affiliation>Department of Biochemical and Cellular Pharmacology, Genentech, San Francisco, CA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biochemical and Cellular Pharmacology, Genentech, San Francisco, CA</wicri:regionArea>
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<region type="state">Californie</region>
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<author>
<name sortKey="Galvez, Eric J C" sort="Galvez, Eric J C" uniqKey="Galvez E" first="Eric J C" last="Gálvez">Eric J C. Gálvez</name>
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<nlm:affiliation>Research Group Microbial Immune Regulation, Helmholtz Centre for Infection Research, Braunschweig, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Research Group Microbial Immune Regulation, Helmholtz Centre for Infection Research, Braunschweig</wicri:regionArea>
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<name sortKey="Stehle, Christina" sort="Stehle, Christina" uniqKey="Stehle C" first="Christina" last="Stehle">Christina Stehle</name>
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<nlm:affiliation>German Rheumatism Research Center (DRFZ) Berlin, Leibniz Association, Berlin, Germany.</nlm:affiliation>
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<name sortKey="Heinz, Gitta A" sort="Heinz, Gitta A" uniqKey="Heinz G" first="Gitta A" last="Heinz">Gitta A. Heinz</name>
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<nlm:affiliation>German Rheumatism Research Center (DRFZ) Berlin, Leibniz Association, Berlin, Germany.</nlm:affiliation>
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<name sortKey="Maschmeyer, Patrick" sort="Maschmeyer, Patrick" uniqKey="Maschmeyer P" first="Patrick" last="Maschmeyer">Patrick Maschmeyer</name>
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<nlm:affiliation>German Rheumatism Research Center (DRFZ) Berlin, Leibniz Association, Berlin, Germany.</nlm:affiliation>
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<author>
<name sortKey="Sidwell, Tom" sort="Sidwell, Tom" uniqKey="Sidwell T" first="Tom" last="Sidwell">Tom Sidwell</name>
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<nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne</wicri:regionArea>
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<settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
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<orgName type="university">Université de Melbourne</orgName>
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<nlm:affiliation>Molecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Molecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne</wicri:regionArea>
<placeName>
<settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
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<author>
<name sortKey="Hu, Yifang" sort="Hu, Yifang" uniqKey="Hu Y" first="Yifang" last="Hu">Yifang Hu</name>
<affiliation wicri:level="4">
<nlm:affiliation>Department of Medical Biology, University of Melbourne, Melbourne, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Biology, University of Melbourne, Melbourne</wicri:regionArea>
<placeName>
<settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
<orgName type="university">Université de Melbourne</orgName>
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<nlm:affiliation>Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne</wicri:regionArea>
<placeName>
<settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
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<name sortKey="Amsen, Derk" sort="Amsen, Derk" uniqKey="Amsen D" first="Derk" last="Amsen">Derk Amsen</name>
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<nlm:affiliation>Sanquin Research, Department of Hematopoiesis and Landsteiner Laboratory, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Sanquin Research, Department of Hematopoiesis and Landsteiner Laboratory, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam</wicri:regionArea>
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<settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
<orgName type="university">Université d'Amsterdam</orgName>
</affiliation>
</author>
<author>
<name sortKey="Romagnani, Chiara" sort="Romagnani, Chiara" uniqKey="Romagnani C" first="Chiara" last="Romagnani">Chiara Romagnani</name>
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<nlm:affiliation>German Rheumatism Research Center (DRFZ) Berlin, Leibniz Association, Berlin, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>German Rheumatism Research Center (DRFZ) Berlin, Leibniz Association, Berlin</wicri:regionArea>
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<region type="land" nuts="3">Berlin</region>
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<nlm:affiliation>Medical Department I, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Medical Department I, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin</wicri:regionArea>
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<region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
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</affiliation>
</author>
<author>
<name sortKey="Chang, Hyun Dong" sort="Chang, Hyun Dong" uniqKey="Chang H" first="Hyun-Dong" last="Chang">Hyun-Dong Chang</name>
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<country xml:lang="fr">Allemagne</country>
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<region type="land" nuts="3">Berlin</region>
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<author>
<name sortKey="Kruglov, Andrey" sort="Kruglov, Andrey" uniqKey="Kruglov A" first="Andrey" last="Kruglov">Andrey Kruglov</name>
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<nlm:affiliation>German Rheumatism Research Center (DRFZ) Berlin, Leibniz Association, Berlin, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
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<region type="land" nuts="3">Berlin</region>
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<affiliation wicri:level="3">
<nlm:affiliation>Belozersky Institute of Physico-Chemical Biology and Biological Faculty, M.V. Lomonosov Moscow State University, Moscow, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Belozersky Institute of Physico-Chemical Biology and Biological Faculty, M.V. Lomonosov Moscow State University, Moscow</wicri:regionArea>
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<settlement type="city">Moscou</settlement>
<region>District fédéral central</region>
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<author>
<name sortKey="Mashreghi, Mir Farzin" sort="Mashreghi, Mir Farzin" uniqKey="Mashreghi M" first="Mir-Farzin" last="Mashreghi">Mir-Farzin Mashreghi</name>
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<nlm:affiliation>German Rheumatism Research Center (DRFZ) Berlin, Leibniz Association, Berlin, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
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<placeName>
<region type="land" nuts="3">Berlin</region>
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<author>
<name sortKey="Shi, Wei" sort="Shi, Wei" uniqKey="Shi W" first="Wei" last="Shi">Wei Shi</name>
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<nlm:affiliation>Department of Medical Biology, University of Melbourne, Melbourne, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Biology, University of Melbourne, Melbourne</wicri:regionArea>
<placeName>
<settlement type="city">Melbourne</settlement>
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</placeName>
<orgName type="university">Université de Melbourne</orgName>
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<nlm:affiliation>Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne</wicri:regionArea>
<placeName>
<settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
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</author>
<author>
<name sortKey="Strowig, Till" sort="Strowig, Till" uniqKey="Strowig T" first="Till" last="Strowig">Till Strowig</name>
<affiliation wicri:level="1">
<nlm:affiliation>Research Group Microbial Immune Regulation, Helmholtz Centre for Infection Research, Braunschweig, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Research Group Microbial Immune Regulation, Helmholtz Centre for Infection Research, Braunschweig</wicri:regionArea>
<wicri:noRegion>Braunschweig</wicri:noRegion>
<wicri:noRegion>Braunschweig</wicri:noRegion>
<wicri:noRegion>Braunschweig</wicri:noRegion>
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<author>
<name sortKey="Rutz, Sascha" sort="Rutz, Sascha" uniqKey="Rutz S" first="Sascha" last="Rutz">Sascha Rutz</name>
<affiliation wicri:level="2">
<nlm:affiliation>Department of Cancer Immunology, Genentech, San Francisco, CA, USA. saschar@gene.com.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Cancer Immunology, Genentech, San Francisco, CA</wicri:regionArea>
<placeName>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Kallies, Axel" sort="Kallies, Axel" uniqKey="Kallies A" first="Axel" last="Kallies">Axel Kallies</name>
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<nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia. axel.kallies@unimelb.edu.au.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne</wicri:regionArea>
<placeName>
<settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
<orgName type="university">Université de Melbourne</orgName>
</affiliation>
<affiliation wicri:level="3">
<nlm:affiliation>Molecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. axel.kallies@unimelb.edu.au.</nlm:affiliation>
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<title xml:lang="en">c-Maf-dependent T
<sub>reg</sub>
cell control of intestinal T
<sub>H</sub>
17 cells and IgA establishes host-microbiota homeostasis.</title>
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<name sortKey="Neumann, Christian" sort="Neumann, Christian" uniqKey="Neumann C" first="Christian" last="Neumann">Christian Neumann</name>
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<nlm:affiliation>Department of Cellular Immunology, Clinic for Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Cellular Immunology, Clinic for Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin</wicri:regionArea>
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<nlm:affiliation>German Rheumatism Research Center (DRFZ) Berlin, Leibniz Association, Berlin, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
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<nlm:affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.</nlm:affiliation>
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<nlm:affiliation>Molecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
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<country xml:lang="fr">Allemagne</country>
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<nlm:affiliation>Department of Medical Biology, University of Melbourne, Melbourne, Australia.</nlm:affiliation>
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<wicri:regionArea>Department of Medical Biology, University of Melbourne, Melbourne</wicri:regionArea>
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<settlement type="city">Melbourne</settlement>
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<country xml:lang="fr">Allemagne</country>
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<nlm:affiliation>Department of Cancer Immunology, Genentech, San Francisco, CA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
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<region type="state">Californie</region>
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<country xml:lang="fr">États-Unis</country>
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<region type="state">Californie</region>
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<nlm:affiliation>Department of Biochemical and Cellular Pharmacology, Genentech, San Francisco, CA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
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<region type="state">Californie</region>
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<nlm:affiliation>Research Group Microbial Immune Regulation, Helmholtz Centre for Infection Research, Braunschweig, Germany.</nlm:affiliation>
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<nlm:affiliation>German Rheumatism Research Center (DRFZ) Berlin, Leibniz Association, Berlin, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
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<nlm:affiliation>German Rheumatism Research Center (DRFZ) Berlin, Leibniz Association, Berlin, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
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<region type="land" nuts="3">Berlin</region>
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<country xml:lang="fr">Allemagne</country>
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<country xml:lang="fr">Australie</country>
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<nlm:affiliation>Department of Medical Biology, University of Melbourne, Melbourne, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
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<country xml:lang="fr">Pays-Bas</country>
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<orgName type="university">Université d'Amsterdam</orgName>
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<nlm:affiliation>German Rheumatism Research Center (DRFZ) Berlin, Leibniz Association, Berlin, Germany.</nlm:affiliation>
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<country xml:lang="fr">Allemagne</country>
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<name sortKey="Shi, Wei" sort="Shi, Wei" uniqKey="Shi W" first="Wei" last="Shi">Wei Shi</name>
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<nlm:affiliation>Department of Medical Biology, University of Melbourne, Melbourne, Australia.</nlm:affiliation>
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<name sortKey="Scheffold, Alexander" sort="Scheffold, Alexander" uniqKey="Scheffold A" first="Alexander" last="Scheffold">Alexander Scheffold</name>
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<nlm:affiliation>Institute of Immunology, Christian-Albrechts-Universität zu Kiel & Universitätsklinik Schleswig Holstein, Kiel, Germany. alexander.scheffold@uksh.de.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
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<settlement type="city">Kiel</settlement>
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</affiliation>
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<series>
<title level="j">Nature immunology</title>
<idno type="eISSN">1529-2916</idno>
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<date when="2019" type="published">2019</date>
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<term>Animals (MeSH)</term>
<term>Cells, Cultured (MeSH)</term>
<term>Colitis (immunology)</term>
<term>Cytokines (metabolism)</term>
<term>Dysbiosis (MeSH)</term>
<term>Gene Expression Regulation (MeSH)</term>
<term>Homeostasis (MeSH)</term>
<term>Immunoglobulin A (biosynthesis)</term>
<term>Interleukin-10 (biosynthesis)</term>
<term>Intestines (immunology)</term>
<term>Mice, Inbred C57BL (MeSH)</term>
<term>Microbiota (MeSH)</term>
<term>Proto-Oncogene Proteins c-maf (genetics)</term>
<term>Proto-Oncogene Proteins c-maf (metabolism)</term>
<term>Proto-Oncogene Proteins c-maf (physiology)</term>
<term>T-Lymphocytes, Regulatory (enzymology)</term>
<term>T-Lymphocytes, Regulatory (immunology)</term>
<term>Th17 Cells (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Animaux (MeSH)</term>
<term>Cellules Th17 (immunologie)</term>
<term>Cellules cultivées (MeSH)</term>
<term>Colite (immunologie)</term>
<term>Cytokines (métabolisme)</term>
<term>Dysbiose (MeSH)</term>
<term>Homéostasie (MeSH)</term>
<term>Immunoglobuline A (biosynthèse)</term>
<term>Interleukine-10 (biosynthèse)</term>
<term>Intestins (immunologie)</term>
<term>Lymphocytes T régulateurs (enzymologie)</term>
<term>Lymphocytes T régulateurs (immunologie)</term>
<term>Microbiote (MeSH)</term>
<term>Protéines proto-oncogènes c-maf (génétique)</term>
<term>Protéines proto-oncogènes c-maf (métabolisme)</term>
<term>Protéines proto-oncogènes c-maf (physiologie)</term>
<term>Régulation de l'expression des gènes (MeSH)</term>
<term>Souris de lignée C57BL (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en">
<term>Immunoglobulin A</term>
<term>Interleukin-10</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>Proto-Oncogene Proteins c-maf</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Cytokines</term>
<term>Proto-Oncogene Proteins c-maf</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr">
<term>Immunoglobuline A</term>
<term>Interleukine-10</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr">
<term>Lymphocytes T régulateurs</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymology" xml:lang="en">
<term>T-Lymphocytes, Regulatory</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Protéines proto-oncogènes c-maf</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Cellules Th17</term>
<term>Colite</term>
<term>Intestins</term>
<term>Lymphocytes T régulateurs</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>Colitis</term>
<term>Intestines</term>
<term>T-Lymphocytes, Regulatory</term>
<term>Th17 Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Cytokines</term>
<term>Protéines proto-oncogènes c-maf</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr">
<term>Protéines proto-oncogènes c-maf</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en">
<term>Proto-Oncogene Proteins c-maf</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Animals</term>
<term>Cells, Cultured</term>
<term>Dysbiosis</term>
<term>Gene Expression Regulation</term>
<term>Homeostasis</term>
<term>Mice, Inbred C57BL</term>
<term>Microbiota</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Animaux</term>
<term>Cellules cultivées</term>
<term>Dysbiose</term>
<term>Homéostasie</term>
<term>Microbiote</term>
<term>Régulation de l'expression des gènes</term>
<term>Souris de lignée C57BL</term>
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<front>
<div type="abstract" xml:lang="en">Foxp3
<sup>+</sup>
regulatory T cells (T
<sub>reg</sub>
cells) are crucial for the maintenance of immune homeostasis both in lymphoid tissues and in non-lymphoid tissues. Here we demonstrate that the ability of intestinal T
<sub>reg</sub>
cells to constrain microbiota-dependent interleukin (IL)-17-producing helper T cell (T
<sub>H</sub>
17 cell) and immunoglobulin A responses critically required expression of the transcription factor c-Maf. The terminal differentiation and function of several intestinal T
<sub>reg</sub>
cell populations, including RORγt
<sup>+</sup>
T
<sub>reg</sub>
cells and follicular regulatory T cells, were c-Maf dependent. c-Maf controlled T
<sub>reg</sub>
cell-derived IL-10 production and prevented excessive signaling via the kinases PI(3)K (phosphatidylinositol-3-OH kinase) and Akt and the metabolic checkpoint kinase complex mTORC1 (mammalian target of rapamycin) and expression of inflammatory cytokines in intestinal T
<sub>reg</sub>
cells. c-Maf deficiency in T
<sub>reg</sub>
cells led to profound dysbiosis of the intestinal microbiota, which when transferred to germ-free mice was sufficient to induce exacerbated intestinal T
<sub>H</sub>
17 responses, even in a c-Maf-competent environment. Thus, c-Maf acts to preserve the identity and function of intestinal T
<sub>reg</sub>
cells, which is essential for the establishment of host-microbe symbiosis.</div>
</front>
</TEI>
<pubmed>
<MedlineCitation Status="MEDLINE" Owner="NLM">
<PMID Version="1">30778241</PMID>
<DateCompleted>
<Year>2019</Year>
<Month>04</Month>
<Day>19</Day>
</DateCompleted>
<DateRevised>
<Year>2020</Year>
<Month>02</Month>
<Day>11</Day>
</DateRevised>
<Article PubModel="Print-Electronic">
<Journal>
<ISSN IssnType="Electronic">1529-2916</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>20</Volume>
<Issue>4</Issue>
<PubDate>
<Year>2019</Year>
<Month>04</Month>
</PubDate>
</JournalIssue>
<Title>Nature immunology</Title>
<ISOAbbreviation>Nat Immunol</ISOAbbreviation>
</Journal>
<ArticleTitle>c-Maf-dependent T
<sub>reg</sub>
cell control of intestinal T
<sub>H</sub>
17 cells and IgA establishes host-microbiota homeostasis.</ArticleTitle>
<Pagination>
<MedlinePgn>471-481</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1038/s41590-019-0316-2</ELocationID>
<Abstract>
<AbstractText>Foxp3
<sup>+</sup>
regulatory T cells (T
<sub>reg</sub>
cells) are crucial for the maintenance of immune homeostasis both in lymphoid tissues and in non-lymphoid tissues. Here we demonstrate that the ability of intestinal T
<sub>reg</sub>
cells to constrain microbiota-dependent interleukin (IL)-17-producing helper T cell (T
<sub>H</sub>
17 cell) and immunoglobulin A responses critically required expression of the transcription factor c-Maf. The terminal differentiation and function of several intestinal T
<sub>reg</sub>
cell populations, including RORγt
<sup>+</sup>
T
<sub>reg</sub>
cells and follicular regulatory T cells, were c-Maf dependent. c-Maf controlled T
<sub>reg</sub>
cell-derived IL-10 production and prevented excessive signaling via the kinases PI(3)K (phosphatidylinositol-3-OH kinase) and Akt and the metabolic checkpoint kinase complex mTORC1 (mammalian target of rapamycin) and expression of inflammatory cytokines in intestinal T
<sub>reg</sub>
cells. c-Maf deficiency in T
<sub>reg</sub>
cells led to profound dysbiosis of the intestinal microbiota, which when transferred to germ-free mice was sufficient to induce exacerbated intestinal T
<sub>H</sub>
17 responses, even in a c-Maf-competent environment. Thus, c-Maf acts to preserve the identity and function of intestinal T
<sub>reg</sub>
cells, which is essential for the establishment of host-microbe symbiosis.</AbstractText>
</Abstract>
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<ForeName>Christian</ForeName>
<Initials>C</Initials>
<AffiliationInfo>
<Affiliation>Department of Cellular Immunology, Clinic for Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>German Rheumatism Research Center (DRFZ) Berlin, Leibniz Association, Berlin, Germany.</Affiliation>
</AffiliationInfo>
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<LastName>Blume</LastName>
<ForeName>Jonas</ForeName>
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<Affiliation>Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.</Affiliation>
</AffiliationInfo>
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<Affiliation>Molecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.</Affiliation>
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<Affiliation>Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.</Affiliation>
</AffiliationInfo>
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<ForeName>Teresita L</ForeName>
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<ForeName>Celine</ForeName>
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<LastName>Gálvez</LastName>
<ForeName>Eric J C</ForeName>
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<AffiliationInfo>
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<ForeName>Sascha</ForeName>
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<Affiliation>Department of Cancer Immunology, Genentech, San Francisco, CA, USA. saschar@gene.com.</Affiliation>
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<MeshHeading>
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<MeshHeading>
<DescriptorName UI="D003092" MajorTopicYN="N">Colitis</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D016207" MajorTopicYN="N">Cytokines</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D064806" MajorTopicYN="N">Dysbiosis</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D005786" MajorTopicYN="N">Gene Expression Regulation</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D006706" MajorTopicYN="N">Homeostasis</DescriptorName>
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<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
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<MeshHeading>
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<Month>10</Month>
<Day>26</Day>
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<Year>2019</Year>
<Month>01</Month>
<Day>07</Day>
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<Month>2</Month>
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<li>Berlin</li>
<li>Kiel</li>
<li>Melbourne</li>
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<name sortKey="Shi, Wei" sort="Shi, Wei" uniqKey="Shi W" first="Wei" last="Shi">Wei Shi</name>
<name sortKey="Shi, Wei" sort="Shi, Wei" uniqKey="Shi W" first="Wei" last="Shi">Wei Shi</name>
<name sortKey="Sidwell, Tom" sort="Sidwell, Tom" uniqKey="Sidwell T" first="Tom" last="Sidwell">Tom Sidwell</name>
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<name sortKey="Teh, Peggy P" sort="Teh, Peggy P" uniqKey="Teh P" first="Peggy P" last="Teh">Peggy P. Teh</name>
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<name sortKey="Vasanthakumar, Ajithkumar" sort="Vasanthakumar, Ajithkumar" uniqKey="Vasanthakumar A" first="Ajithkumar" last="Vasanthakumar">Ajithkumar Vasanthakumar</name>
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<name sortKey="Arenzana, Teresita L" sort="Arenzana, Teresita L" uniqKey="Arenzana T" first="Teresita L" last="Arenzana">Teresita L. Arenzana</name>
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