Anti-apoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3+ regulatory T cells
Identifieur interne : 001D75 ( Pmc/Corpus ); précédent : 001D74; suivant : 001D76Anti-apoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3+ regulatory T cells
Auteurs : Wim Pierson ; Bénédicte Cauwe ; Antonia Policheni ; Susan M. Schlenner ; Dean Franckaert ; Julien Berges ; Stephanie Humblet-Baron ; Susann Schonefeldt ; Marco J. Herold ; David Hildeman ; Andreas Strasser ; Philippe Bouillet ; Li-Fan Lu ; Patrick Matthys ; Antonio A. Freitas ; Rita J. Luther ; Casey T. Weaver ; James Dooley ; Daniel H. D. Gray ; Adrian ListonSource :
- Nature immunology [ 1529-2908 ] ; 2013.
Abstract
Foxp3+ regulatory T (Treg) cells are a crucial immunosuppressive population of CD4+ T cells, yet the homeostatic processes and survival programs that maintain the Treg cell pool are poorly understood. Here we report that peripheral Treg cells markedly alter their proliferative and apoptotic rates to rapidly restore numerical deficit through an interleukin 2–dependent and costimulation-dependent process. By contrast, excess Treg cells are removed by attrition, dependent on the Bim-initiated Bak- and Bax-dependent intrinsic apoptotic pathway. The antiapoptotic proteins Bcl-xL and Bcl-2 were dispensable for survival of Treg cells, whereas Mcl-1 was critical for survival of Treg cells, and the loss of this antiapoptotic protein caused fatal autoimmunity. Together, these data define the active processes by which Treg cells maintain homeostasis via critical survival pathways.
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DOI: 10.1038/ni.2649
PubMed: 23852275
PubMed Central: 4128388
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PMC:4128388Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Anti-apoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3<sup>+</sup> regulatory T cells</title><author><name sortKey="Pierson, Wim" sort="Pierson, Wim" uniqKey="Pierson W" first="Wim" last="Pierson">Wim Pierson</name><affiliation><nlm:aff id="A1">Autoimmune Genetics Laboratory, VIB, Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Cauwe, Benedicte" sort="Cauwe, Benedicte" uniqKey="Cauwe B" first="Bénédicte" last="Cauwe">Bénédicte Cauwe</name><affiliation><nlm:aff id="A1">Autoimmune Genetics Laboratory, VIB, Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Policheni, Antonia" sort="Policheni, Antonia" uniqKey="Policheni A" first="Antonia" last="Policheni">Antonia Policheni</name><affiliation><nlm:aff id="A3">The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Medical Biology, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Schlenner, Susan M" sort="Schlenner, Susan M" uniqKey="Schlenner S" first="Susan M." last="Schlenner">Susan M. Schlenner</name><affiliation><nlm:aff id="A1">Autoimmune Genetics Laboratory, VIB, Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Franckaert, Dean" sort="Franckaert, Dean" uniqKey="Franckaert D" first="Dean" last="Franckaert">Dean Franckaert</name><affiliation><nlm:aff id="A1">Autoimmune Genetics Laboratory, VIB, Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Berges, Julien" sort="Berges, Julien" uniqKey="Berges J" first="Julien" last="Berges">Julien Berges</name><affiliation><nlm:aff id="A5">Unité de Biologie des Populations Lymphocytaires, Department of Immunology, Institut Pasteur, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Centre national de la recherché scientifique, URA 1961, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Humblet Baron, Stephanie" sort="Humblet Baron, Stephanie" uniqKey="Humblet Baron S" first="Stephanie" last="Humblet-Baron">Stephanie Humblet-Baron</name><affiliation><nlm:aff id="A1">Autoimmune Genetics Laboratory, VIB, Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Schonefeldt, Susann" sort="Schonefeldt, Susann" uniqKey="Schonefeldt S" first="Susann" last="Schonefeldt">Susann Schonefeldt</name><affiliation><nlm:aff id="A1">Autoimmune Genetics Laboratory, VIB, Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Herold, Marco J" sort="Herold, Marco J" uniqKey="Herold M" first="Marco J." last="Herold">Marco J. Herold</name><affiliation><nlm:aff id="A3">The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Medical Biology, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Hildeman, David" sort="Hildeman, David" uniqKey="Hildeman D" first="David" last="Hildeman">David Hildeman</name><affiliation><nlm:aff id="A7">Division of Immunobiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Children’s Hospital Medical Center, Cincinnati, Ohio, USA</nlm:aff></affiliation></author><author><name sortKey="Strasser, Andreas" sort="Strasser, Andreas" uniqKey="Strasser A" first="Andreas" last="Strasser">Andreas Strasser</name><affiliation><nlm:aff id="A3">The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Medical Biology, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Bouillet, Philippe" sort="Bouillet, Philippe" uniqKey="Bouillet P" first="Philippe" last="Bouillet">Philippe Bouillet</name><affiliation><nlm:aff id="A3">The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Medical Biology, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Lu, Li Fan" sort="Lu, Li Fan" uniqKey="Lu L" first="Li-Fan" last="Lu">Li-Fan Lu</name><affiliation><nlm:aff id="A9">Section of Molecular Biology, Division of Biological Sciences, University of California–San Diego, La Jolla, California, USA</nlm:aff></affiliation></author><author><name sortKey="Matthys, Patrick" sort="Matthys, Patrick" uniqKey="Matthys P" first="Patrick" last="Matthys">Patrick Matthys</name><affiliation><nlm:aff id="A10">Laboratory of Immunobiology, Rega Institute, University of Leuven, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Freitas, Antonio A" sort="Freitas, Antonio A" uniqKey="Freitas A" first="Antonio A." last="Freitas">Antonio A. Freitas</name><affiliation><nlm:aff id="A5">Unité de Biologie des Populations Lymphocytaires, Department of Immunology, Institut Pasteur, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Centre national de la recherché scientifique, URA 1961, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Luther, Rita J" sort="Luther, Rita J" uniqKey="Luther R" first="Rita J." last="Luther">Rita J. Luther</name><affiliation><nlm:aff id="A11">Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA</nlm:aff></affiliation></author><author><name sortKey="Weaver, Casey T" sort="Weaver, Casey T" uniqKey="Weaver C" first="Casey T." last="Weaver">Casey T. Weaver</name><affiliation><nlm:aff id="A11">Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA</nlm:aff></affiliation></author><author><name sortKey="Dooley, James" sort="Dooley, James" uniqKey="Dooley J" first="James" last="Dooley">James Dooley</name><affiliation><nlm:aff id="A1">Autoimmune Genetics Laboratory, VIB, Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Gray, Daniel H D" sort="Gray, Daniel H D" uniqKey="Gray D" first="Daniel H. D." last="Gray">Daniel H. D. Gray</name><affiliation><nlm:aff id="A3">The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Medical Biology, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Liston, Adrian" sort="Liston, Adrian" uniqKey="Liston A" first="Adrian" last="Liston">Adrian Liston</name><affiliation><nlm:aff id="A1">Autoimmune Genetics Laboratory, VIB, Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23852275</idno><idno type="pmc">4128388</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128388</idno><idno type="RBID">PMC:4128388</idno><idno type="doi">10.1038/ni.2649</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">001D75</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001D75</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Anti-apoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3<sup>+</sup> regulatory T cells</title><author><name sortKey="Pierson, Wim" sort="Pierson, Wim" uniqKey="Pierson W" first="Wim" last="Pierson">Wim Pierson</name><affiliation><nlm:aff id="A1">Autoimmune Genetics Laboratory, VIB, Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Cauwe, Benedicte" sort="Cauwe, Benedicte" uniqKey="Cauwe B" first="Bénédicte" last="Cauwe">Bénédicte Cauwe</name><affiliation><nlm:aff id="A1">Autoimmune Genetics Laboratory, VIB, Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Policheni, Antonia" sort="Policheni, Antonia" uniqKey="Policheni A" first="Antonia" last="Policheni">Antonia Policheni</name><affiliation><nlm:aff id="A3">The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Medical Biology, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Schlenner, Susan M" sort="Schlenner, Susan M" uniqKey="Schlenner S" first="Susan M." last="Schlenner">Susan M. Schlenner</name><affiliation><nlm:aff id="A1">Autoimmune Genetics Laboratory, VIB, Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Franckaert, Dean" sort="Franckaert, Dean" uniqKey="Franckaert D" first="Dean" last="Franckaert">Dean Franckaert</name><affiliation><nlm:aff id="A1">Autoimmune Genetics Laboratory, VIB, Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Berges, Julien" sort="Berges, Julien" uniqKey="Berges J" first="Julien" last="Berges">Julien Berges</name><affiliation><nlm:aff id="A5">Unité de Biologie des Populations Lymphocytaires, Department of Immunology, Institut Pasteur, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Centre national de la recherché scientifique, URA 1961, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Humblet Baron, Stephanie" sort="Humblet Baron, Stephanie" uniqKey="Humblet Baron S" first="Stephanie" last="Humblet-Baron">Stephanie Humblet-Baron</name><affiliation><nlm:aff id="A1">Autoimmune Genetics Laboratory, VIB, Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Schonefeldt, Susann" sort="Schonefeldt, Susann" uniqKey="Schonefeldt S" first="Susann" last="Schonefeldt">Susann Schonefeldt</name><affiliation><nlm:aff id="A1">Autoimmune Genetics Laboratory, VIB, Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Herold, Marco J" sort="Herold, Marco J" uniqKey="Herold M" first="Marco J." last="Herold">Marco J. Herold</name><affiliation><nlm:aff id="A3">The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Medical Biology, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Hildeman, David" sort="Hildeman, David" uniqKey="Hildeman D" first="David" last="Hildeman">David Hildeman</name><affiliation><nlm:aff id="A7">Division of Immunobiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Children’s Hospital Medical Center, Cincinnati, Ohio, USA</nlm:aff></affiliation></author><author><name sortKey="Strasser, Andreas" sort="Strasser, Andreas" uniqKey="Strasser A" first="Andreas" last="Strasser">Andreas Strasser</name><affiliation><nlm:aff id="A3">The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Medical Biology, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Bouillet, Philippe" sort="Bouillet, Philippe" uniqKey="Bouillet P" first="Philippe" last="Bouillet">Philippe Bouillet</name><affiliation><nlm:aff id="A3">The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Medical Biology, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Lu, Li Fan" sort="Lu, Li Fan" uniqKey="Lu L" first="Li-Fan" last="Lu">Li-Fan Lu</name><affiliation><nlm:aff id="A9">Section of Molecular Biology, Division of Biological Sciences, University of California–San Diego, La Jolla, California, USA</nlm:aff></affiliation></author><author><name sortKey="Matthys, Patrick" sort="Matthys, Patrick" uniqKey="Matthys P" first="Patrick" last="Matthys">Patrick Matthys</name><affiliation><nlm:aff id="A10">Laboratory of Immunobiology, Rega Institute, University of Leuven, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Freitas, Antonio A" sort="Freitas, Antonio A" uniqKey="Freitas A" first="Antonio A." last="Freitas">Antonio A. Freitas</name><affiliation><nlm:aff id="A5">Unité de Biologie des Populations Lymphocytaires, Department of Immunology, Institut Pasteur, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Centre national de la recherché scientifique, URA 1961, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Luther, Rita J" sort="Luther, Rita J" uniqKey="Luther R" first="Rita J." last="Luther">Rita J. Luther</name><affiliation><nlm:aff id="A11">Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA</nlm:aff></affiliation></author><author><name sortKey="Weaver, Casey T" sort="Weaver, Casey T" uniqKey="Weaver C" first="Casey T." last="Weaver">Casey T. Weaver</name><affiliation><nlm:aff id="A11">Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA</nlm:aff></affiliation></author><author><name sortKey="Dooley, James" sort="Dooley, James" uniqKey="Dooley J" first="James" last="Dooley">James Dooley</name><affiliation><nlm:aff id="A1">Autoimmune Genetics Laboratory, VIB, Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Gray, Daniel H D" sort="Gray, Daniel H D" uniqKey="Gray D" first="Daniel H. D." last="Gray">Daniel H. D. Gray</name><affiliation><nlm:aff id="A3">The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Medical Biology, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Liston, Adrian" sort="Liston, Adrian" uniqKey="Liston A" first="Adrian" last="Liston">Adrian Liston</name><affiliation><nlm:aff id="A1">Autoimmune Genetics Laboratory, VIB, Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium</nlm:aff></affiliation></author></analytic><series><title level="j">Nature immunology</title><idno type="ISSN">1529-2908</idno><idno type="eISSN">1529-2916</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Foxp3<sup>+</sup> regulatory T (T<sub>reg</sub>) cells are a crucial immunosuppressive population of CD4<sup>+</sup> T cells, yet the homeostatic processes and survival programs that maintain the T<sub>reg</sub> cell pool are poorly understood. Here we report that peripheral T<sub>reg</sub> cells markedly alter their proliferative and apoptotic rates to rapidly restore numerical deficit through an interleukin 2–dependent and costimulation-dependent process. By contrast, excess T<sub>reg</sub> cells are removed by attrition, dependent on the Bim-initiated Bak- and Bax-dependent intrinsic apoptotic pathway. The antiapoptotic proteins Bcl-x<sub>L</sub> and Bcl-2 were dispensable for survival of T<sub>reg</sub> cells, whereas Mcl-1 was critical for survival of T<sub>reg</sub> cells, and the loss of this antiapoptotic protein caused fatal autoimmunity. Together, these data define the active processes by which T<sub>reg</sub> cells maintain homeostasis via critical survival pathways.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">100941354</journal-id><journal-id journal-id-type="pubmed-jr-id">21750</journal-id><journal-id journal-id-type="nlm-ta">Nat Immunol</journal-id><journal-id journal-id-type="iso-abbrev">Nat. Immunol.</journal-id><journal-title-group><journal-title>Nature immunology</journal-title></journal-title-group><issn pub-type="ppub">1529-2908</issn><issn pub-type="epub">1529-2916</issn></journal-meta><article-meta><article-id pub-id-type="pmid">23852275</article-id><article-id pub-id-type="pmc">4128388</article-id><article-id pub-id-type="doi">10.1038/ni.2649</article-id><article-id pub-id-type="manuscript">NIHMS608202</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Anti-apoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3<sup>+</sup> regulatory T cells</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Pierson</surname><given-names>Wim</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Cauwe</surname><given-names>Bénédicte</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Policheni</surname><given-names>Antonia</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Schlenner</surname><given-names>Susan M.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Franckaert</surname><given-names>Dean</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Berges</surname><given-names>Julien</given-names></name><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Humblet-Baron</surname><given-names>Stephanie</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Schonefeldt</surname><given-names>Susann</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Herold</surname><given-names>Marco J.</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Hildeman</surname><given-names>David</given-names></name><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Strasser</surname><given-names>Andreas</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Bouillet</surname><given-names>Philippe</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Lu</surname><given-names>Li-Fan</given-names></name><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Matthys</surname><given-names>Patrick</given-names></name><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Freitas</surname><given-names>Antonio A.</given-names></name><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Luther</surname><given-names>Rita J.</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Weaver</surname><given-names>Casey T.</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Dooley</surname><given-names>James</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Gray</surname><given-names>Daniel H. D.</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A4">4</xref><xref rid="FN2" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Liston</surname><given-names>Adrian</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref rid="FN2" ref-type="author-notes">*</xref></contrib></contrib-group><aff id="A1"><label>1</label>Autoimmune Genetics Laboratory, VIB, Leuven, Belgium</aff><aff id="A2"><label>2</label>Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium</aff><aff id="A3"><label>3</label>The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia</aff><aff id="A4"><label>4</label>Department of Medical Biology, University of Melbourne, Melbourne, Australia</aff><aff id="A5"><label>5</label>Unité de Biologie des Populations Lymphocytaires, Department of Immunology, Institut Pasteur, Paris, France</aff><aff id="A6"><label>6</label>Centre national de la recherché scientifique, URA 1961, Paris, France</aff><aff id="A7"><label>7</label>Division of Immunobiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA</aff><aff id="A8"><label>8</label>Children’s Hospital Medical Center, Cincinnati, Ohio, USA</aff><aff id="A9"><label>9</label>Section of Molecular Biology, Division of Biological Sciences, University of California–San Diego, La Jolla, California, USA</aff><aff id="A10"><label>10</label>Laboratory of Immunobiology, Rega Institute, University of Leuven, Leuven, Belgium</aff><aff id="A11"><label>11</label>Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA</aff><author-notes><corresp id="FN1">Correspondence should be addressed to A.L. (<email>adrian.liston@vib.be</email>) or D.H.D.G. (<email>dgray@wehi.edu.au</email>)</corresp><fn id="FN2" fn-type="equal"><label>*</label><p>These authors contributed equally to this work.</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>25</day><month>6</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>14</day><month>7</month><year>2013</year></pub-date><pub-date pub-type="ppub"><month>9</month><year>2013</year></pub-date><pub-date pub-type="pmc-release"><day>11</day><month>8</month><year>2014</year></pub-date><volume>14</volume><issue>9</issue><fpage>959</fpage><lpage>965</lpage><pmc-comment>elocation-id from pubmed: 10.1038/ni.2649</pmc-comment>
<abstract><p id="P1">Foxp3<sup>+</sup> regulatory T (T<sub>reg</sub>) cells are a crucial immunosuppressive population of CD4<sup>+</sup> T cells, yet the homeostatic processes and survival programs that maintain the T<sub>reg</sub> cell pool are poorly understood. Here we report that peripheral T<sub>reg</sub> cells markedly alter their proliferative and apoptotic rates to rapidly restore numerical deficit through an interleukin 2–dependent and costimulation-dependent process. By contrast, excess T<sub>reg</sub> cells are removed by attrition, dependent on the Bim-initiated Bak- and Bax-dependent intrinsic apoptotic pathway. The antiapoptotic proteins Bcl-x<sub>L</sub> and Bcl-2 were dispensable for survival of T<sub>reg</sub> cells, whereas Mcl-1 was critical for survival of T<sub>reg</sub> cells, and the loss of this antiapoptotic protein caused fatal autoimmunity. Together, these data define the active processes by which T<sub>reg</sub> cells maintain homeostasis via critical survival pathways.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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