TGF-β inhibits the activation and functions of NK cells by repressing the mTOR pathway.
Identifieur interne : 001671 ( Main/Exploration ); précédent : 001670; suivant : 001672TGF-β inhibits the activation and functions of NK cells by repressing the mTOR pathway.
Auteurs : Sébastien Viel [France] ; Antoine Marçais [France] ; Fernando Souza-Fonseca Guimaraes [Australie] ; Roisin Loftus [Irlande (pays)] ; Jessica Rabilloud [France] ; Morgan Grau [France] ; Sophie Degouve [France] ; Sophia Djebali [France] ; Amélien Sanlaville [France] ; Emily Charrier [France] ; Jacques Bienvenu [France] ; Julien C. Marie [Allemagne] ; Christophe Caux [France] ; Jacqueline Marvel [France] ; Liam Town [Australie] ; Nicholas D. Huntington [Australie] ; Laurent Bartholin [France] ; David Finlay [Irlande (pays)] ; Mark J. Smyth [Australie] ; Thierry Walzer [France]Source :
- Science signaling [ 1937-9145 ] ; 2016.
Descripteurs français
- KwdFr :
- Activation des lymphocytes, Animaux, Cellules tueuses naturelles (anatomopathologie), Cellules tueuses naturelles (immunologie), Facteur de croissance transformant bêta (génétique), Facteur de croissance transformant bêta (immunologie), Humains, Immunité cellulaire, Interleukine-15 (immunologie), Souris, Souris knockout, Sérine-thréonine kinases TOR (génétique), Sérine-thréonine kinases TOR (immunologie), Transduction du signal (immunologie), Tumeurs expérimentales (génétique), Tumeurs expérimentales (immunologie).
- MESH :
- anatomopathologie : Cellules tueuses naturelles.
- génétique : Facteur de croissance transformant bêta, Sérine-thréonine kinases TOR, Tumeurs expérimentales.
- immunologie : Cellules tueuses naturelles, Facteur de croissance transformant bêta, Interleukine-15, Sérine-thréonine kinases TOR, Transduction du signal, Tumeurs expérimentales.
- Activation des lymphocytes, Animaux, Humains, Immunité cellulaire, Souris, Souris knockout.
English descriptors
- KwdEn :
- Animals, Humans, Immunity, Cellular, Interleukin-15 (immunology), Killer Cells, Natural (immunology), Killer Cells, Natural (pathology), Lymphocyte Activation, Mice, Mice, Knockout, Neoplasms, Experimental (genetics), Neoplasms, Experimental (immunology), Signal Transduction (immunology), TOR Serine-Threonine Kinases (genetics), TOR Serine-Threonine Kinases (immunology), Transforming Growth Factor beta (genetics), Transforming Growth Factor beta (immunology).
- MESH :
- chemical , genetics : TOR Serine-Threonine Kinases, Transforming Growth Factor beta.
- chemical , immunology : Interleukin-15, TOR Serine-Threonine Kinases, Transforming Growth Factor beta.
- genetics : Neoplasms, Experimental.
- immunology : Killer Cells, Natural, Neoplasms, Experimental, Signal Transduction.
- pathology : Killer Cells, Natural.
- Animals, Humans, Immunity, Cellular, Lymphocyte Activation, Mice, Mice, Knockout.
Abstract
Transforming growth factor-β (TGF-β) is a major immunosuppressive cytokine that maintains immune homeostasis and prevents autoimmunity through its antiproliferative and anti-inflammatory properties in various immune cell types. We provide genetic, pharmacologic, and biochemical evidence that a critical target of TGF-β signaling in mouse and human natural killer (NK) cells is the serine and threonine kinase mTOR (mammalian target of rapamycin). Treatment of mouse or human NK cells with TGF-β in vitro blocked interleukin-15 (IL-15)-induced activation of mTOR. TGF-β and the mTOR inhibitor rapamycin both reduced the metabolic activity and proliferation of NK cells and reduced the abundances of various NK cell receptors and the cytotoxic activity of NK cells. In vivo, constitutive TGF-β signaling or depletion of mTOR arrested NK cell development, whereas deletion of the TGF-β receptor subunit TGF-βRII enhanced mTOR activity and the cytotoxic activity of the NK cells in response to IL-15. Suppression of TGF-β signaling in NK cells did not affect either NK cell development or homeostasis; however, it enhanced the ability of NK cells to limit metastases in two different tumor models in mice. Together, these results suggest that the kinase mTOR is a crucial signaling integrator of pro- and anti-inflammatory cytokines in NK cells. Moreover, we propose that boosting the metabolic activity of antitumor lymphocytes could be an effective strategy to promote immune-mediated tumor suppression.
DOI: 10.1126/scisignal.aad1884
PubMed: 26884601
Affiliations:
- Allemagne, Australie, France, Irlande (pays)
- Auvergne-Rhône-Alpes, Bade-Wurtemberg, District de Karlsruhe, Rhône-Alpes, Victoria (État)
- Heidelberg, Lyon, Melbourne
- Université de Melbourne
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Le document en format XML
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INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon</wicri:regionArea><wicri:noRegion>69007 Lyon</wicri:noRegion><placeName><settlement type="city">Lyon</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Degouve, Sophie" sort="Degouve, Sophie" uniqKey="Degouve S" first="Sophie" last="Degouve">Sophie Degouve</name><affiliation wicri:level="1"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon</wicri:regionArea><wicri:noRegion>69007 Lyon</wicri:noRegion><placeName><settlement type="city">Lyon</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Djebali, Sophia" sort="Djebali, Sophia" uniqKey="Djebali S" first="Sophia" last="Djebali">Sophia Djebali</name><affiliation wicri:level="1"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon</wicri:regionArea><wicri:noRegion>69007 Lyon</wicri:noRegion><placeName><settlement type="city">Lyon</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Sanlaville, Amelien" sort="Sanlaville, Amelien" uniqKey="Sanlaville A" first="Amélien" last="Sanlaville">Amélien Sanlaville</name><affiliation wicri:level="1"><nlm:affiliation>Immunology Virology and Inflammation Department, INSERM U1052, CNRS 5286 Centre de Recherche en Cancérologie de Lyon, 69008 Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Immunology Virology and Inflammation Department, INSERM U1052, CNRS 5286 Centre de Recherche en Cancérologie de Lyon, 69008 Lyon</wicri:regionArea><wicri:noRegion>69008 Lyon</wicri:noRegion><placeName><settlement type="city">Lyon</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Charrier, Emily" sort="Charrier, Emily" uniqKey="Charrier E" first="Emily" last="Charrier">Emily Charrier</name><affiliation wicri:level="1"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France. Laboratoire d'Immunologie, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite 69310, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France. Laboratoire d'Immunologie, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite 69310</wicri:regionArea><wicri:noRegion>69310</wicri:noRegion><wicri:noRegion>69310</wicri:noRegion></affiliation></author><author><name sortKey="Bienvenu, Jacques" sort="Bienvenu, Jacques" uniqKey="Bienvenu J" first="Jacques" last="Bienvenu">Jacques Bienvenu</name><affiliation wicri:level="1"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France. Laboratoire d'Immunologie, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite 69310, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France. Laboratoire d'Immunologie, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite 69310</wicri:regionArea><wicri:noRegion>69310</wicri:noRegion><wicri:noRegion>69310</wicri:noRegion></affiliation></author><author><name sortKey="Marie, Julien C" sort="Marie, Julien C" uniqKey="Marie J" first="Julien C" last="Marie">Julien C. Marie</name><affiliation wicri:level="3"><nlm:affiliation>Immunology Virology and Inflammation Department, INSERM U1052, CNRS 5286 Centre de Recherche en Cancérologie de Lyon, 69008 Lyon, France. TGF-beta and immunoregulation group, DKFZ, Heidelberg 69121, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Immunology Virology and Inflammation Department, INSERM U1052, CNRS 5286 Centre de Recherche en Cancérologie de Lyon, 69008 Lyon, France. TGF-beta and immunoregulation group, DKFZ, Heidelberg 69121</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Caux, Christophe" sort="Caux, Christophe" uniqKey="Caux C" first="Christophe" last="Caux">Christophe Caux</name><affiliation wicri:level="1"><nlm:affiliation>Immunology Virology and Inflammation Department, INSERM U1052, CNRS 5286 Centre de Recherche en Cancérologie de Lyon, 69008 Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Immunology Virology and Inflammation Department, INSERM U1052, CNRS 5286 Centre de Recherche en Cancérologie de Lyon, 69008 Lyon</wicri:regionArea><wicri:noRegion>69008 Lyon</wicri:noRegion><placeName><settlement type="city">Lyon</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Marvel, Jacqueline" sort="Marvel, Jacqueline" uniqKey="Marvel J" first="Jacqueline" last="Marvel">Jacqueline Marvel</name><affiliation wicri:level="1"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon</wicri:regionArea><wicri:noRegion>69007 Lyon</wicri:noRegion><placeName><settlement type="city">Lyon</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Town, Liam" sort="Town, Liam" uniqKey="Town L" first="Liam" last="Town">Liam Town</name><affiliation wicri:level="1"><nlm:affiliation>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland 4006</wicri:regionArea><wicri:noRegion>Queensland 4006</wicri:noRegion></affiliation></author><author><name sortKey="Huntington, Nicholas D" sort="Huntington, Nicholas D" uniqKey="Huntington N" first="Nicholas D" last="Huntington">Nicholas D. Huntington</name><affiliation wicri:level="4"><nlm:affiliation>The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Bartholin, Laurent" sort="Bartholin, Laurent" uniqKey="Bartholin L" first="Laurent" last="Bartholin">Laurent Bartholin</name><affiliation wicri:level="1"><nlm:affiliation>Immunology Virology and Inflammation Department, INSERM U1052, CNRS 5286 Centre de Recherche en Cancérologie de Lyon, 69008 Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Immunology Virology and Inflammation Department, INSERM U1052, CNRS 5286 Centre de Recherche en Cancérologie de Lyon, 69008 Lyon</wicri:regionArea><wicri:noRegion>69008 Lyon</wicri:noRegion><placeName><settlement type="city">Lyon</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Finlay, David" sort="Finlay, David" uniqKey="Finlay D" first="David" last="Finlay">David Finlay</name><affiliation wicri:level="1"><nlm:affiliation>School of Biochemistry and Immunology and School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.</nlm:affiliation><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>School of Biochemistry and Immunology and School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2</wicri:regionArea><wicri:noRegion>Dublin 2</wicri:noRegion></affiliation></author><author><name sortKey="Smyth, Mark J" sort="Smyth, Mark J" uniqKey="Smyth M" first="Mark J" last="Smyth">Mark J. Smyth</name><affiliation wicri:level="1"><nlm:affiliation>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia. School of Medicine, The University of Queensland, Herston, Queensland 4006, Australia. mark.smyth@qimrberghofer.edu.au thierry.walzer@inserm.fr.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia. School of Medicine, The University of Queensland, Herston, Queensland 4006</wicri:regionArea><wicri:noRegion>Queensland 4006</wicri:noRegion></affiliation></author><author><name sortKey="Walzer, Thierry" sort="Walzer, Thierry" uniqKey="Walzer T" first="Thierry" last="Walzer">Thierry Walzer</name><affiliation wicri:level="1"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France. mark.smyth@qimrberghofer.edu.au thierry.walzer@inserm.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon</wicri:regionArea><wicri:noRegion>69007 Lyon</wicri:noRegion><placeName><settlement type="city">Lyon</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:26884601</idno><idno type="pmid">26884601</idno><idno type="doi">10.1126/scisignal.aad1884</idno><idno type="wicri:Area/PubMed/Corpus">002293</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002293</idno><idno type="wicri:Area/PubMed/Curation">002267</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002267</idno><idno type="wicri:Area/PubMed/Checkpoint">002267</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002267</idno><idno type="wicri:Area/Ncbi/Merge">003144</idno><idno type="wicri:Area/Ncbi/Curation">003144</idno><idno type="wicri:Area/Ncbi/Checkpoint">003144</idno><idno type="wicri:Area/Main/Merge">001666</idno><idno type="wicri:Area/Main/Curation">001671</idno><idno type="wicri:Area/Main/Exploration">001671</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">TGF-β inhibits the activation and functions of NK cells by repressing the mTOR pathway.</title><author><name sortKey="Viel, Sebastien" sort="Viel, Sebastien" uniqKey="Viel S" first="Sébastien" last="Viel">Sébastien Viel</name><affiliation wicri:level="3"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France. Laboratoire d'Immunologie, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite 69310, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France. Laboratoire d'Immunologie, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite 69310</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Marcais, Antoine" sort="Marcais, Antoine" uniqKey="Marcais A" first="Antoine" last="Marçais">Antoine Marçais</name><affiliation wicri:level="3"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Guimaraes, Fernando Souza Fonseca" sort="Guimaraes, Fernando Souza Fonseca" uniqKey="Guimaraes F" first="Fernando Souza-Fonseca" last="Guimaraes">Fernando Souza-Fonseca Guimaraes</name><affiliation wicri:level="1"><nlm:affiliation>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia. School of Medicine, The University of Queensland, Herston, Queensland 4006, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia. School of Medicine, The University of Queensland, Herston, Queensland 4006</wicri:regionArea><wicri:noRegion>Queensland 4006</wicri:noRegion></affiliation></author><author><name sortKey="Loftus, Roisin" sort="Loftus, Roisin" uniqKey="Loftus R" first="Roisin" last="Loftus">Roisin Loftus</name><affiliation wicri:level="1"><nlm:affiliation>School of Biochemistry and Immunology and School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.</nlm:affiliation><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>School of Biochemistry and Immunology and School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2</wicri:regionArea><wicri:noRegion>Dublin 2</wicri:noRegion></affiliation></author><author><name sortKey="Rabilloud, Jessica" sort="Rabilloud, Jessica" uniqKey="Rabilloud J" first="Jessica" last="Rabilloud">Jessica Rabilloud</name><affiliation wicri:level="1"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon</wicri:regionArea><wicri:noRegion>69007 Lyon</wicri:noRegion><placeName><settlement type="city">Lyon</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Grau, Morgan" sort="Grau, Morgan" uniqKey="Grau M" first="Morgan" last="Grau">Morgan Grau</name><affiliation wicri:level="1"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon</wicri:regionArea><wicri:noRegion>69007 Lyon</wicri:noRegion><placeName><settlement type="city">Lyon</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Degouve, Sophie" sort="Degouve, Sophie" uniqKey="Degouve S" first="Sophie" last="Degouve">Sophie Degouve</name><affiliation wicri:level="1"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon</wicri:regionArea><wicri:noRegion>69007 Lyon</wicri:noRegion><placeName><settlement type="city">Lyon</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Djebali, Sophia" sort="Djebali, Sophia" uniqKey="Djebali S" first="Sophia" last="Djebali">Sophia Djebali</name><affiliation wicri:level="1"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon</wicri:regionArea><wicri:noRegion>69007 Lyon</wicri:noRegion><placeName><settlement type="city">Lyon</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Sanlaville, Amelien" sort="Sanlaville, Amelien" uniqKey="Sanlaville A" first="Amélien" last="Sanlaville">Amélien Sanlaville</name><affiliation wicri:level="1"><nlm:affiliation>Immunology Virology and Inflammation Department, INSERM U1052, CNRS 5286 Centre de Recherche en Cancérologie de Lyon, 69008 Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Immunology Virology and Inflammation Department, INSERM U1052, CNRS 5286 Centre de Recherche en Cancérologie de Lyon, 69008 Lyon</wicri:regionArea><wicri:noRegion>69008 Lyon</wicri:noRegion><placeName><settlement type="city">Lyon</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Charrier, Emily" sort="Charrier, Emily" uniqKey="Charrier E" first="Emily" last="Charrier">Emily Charrier</name><affiliation wicri:level="1"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France. Laboratoire d'Immunologie, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite 69310, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France. Laboratoire d'Immunologie, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite 69310</wicri:regionArea><wicri:noRegion>69310</wicri:noRegion><wicri:noRegion>69310</wicri:noRegion></affiliation></author><author><name sortKey="Bienvenu, Jacques" sort="Bienvenu, Jacques" uniqKey="Bienvenu J" first="Jacques" last="Bienvenu">Jacques Bienvenu</name><affiliation wicri:level="1"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France. Laboratoire d'Immunologie, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite 69310, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France. Laboratoire d'Immunologie, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite 69310</wicri:regionArea><wicri:noRegion>69310</wicri:noRegion><wicri:noRegion>69310</wicri:noRegion></affiliation></author><author><name sortKey="Marie, Julien C" sort="Marie, Julien C" uniqKey="Marie J" first="Julien C" last="Marie">Julien C. Marie</name><affiliation wicri:level="3"><nlm:affiliation>Immunology Virology and Inflammation Department, INSERM U1052, CNRS 5286 Centre de Recherche en Cancérologie de Lyon, 69008 Lyon, France. TGF-beta and immunoregulation group, DKFZ, Heidelberg 69121, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Immunology Virology and Inflammation Department, INSERM U1052, CNRS 5286 Centre de Recherche en Cancérologie de Lyon, 69008 Lyon, France. TGF-beta and immunoregulation group, DKFZ, Heidelberg 69121</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Caux, Christophe" sort="Caux, Christophe" uniqKey="Caux C" first="Christophe" last="Caux">Christophe Caux</name><affiliation wicri:level="1"><nlm:affiliation>Immunology Virology and Inflammation Department, INSERM U1052, CNRS 5286 Centre de Recherche en Cancérologie de Lyon, 69008 Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Immunology Virology and Inflammation Department, INSERM U1052, CNRS 5286 Centre de Recherche en Cancérologie de Lyon, 69008 Lyon</wicri:regionArea><wicri:noRegion>69008 Lyon</wicri:noRegion><placeName><settlement type="city">Lyon</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Marvel, Jacqueline" sort="Marvel, Jacqueline" uniqKey="Marvel J" first="Jacqueline" last="Marvel">Jacqueline Marvel</name><affiliation wicri:level="1"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon</wicri:regionArea><wicri:noRegion>69007 Lyon</wicri:noRegion><placeName><settlement type="city">Lyon</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Town, Liam" sort="Town, Liam" uniqKey="Town L" first="Liam" last="Town">Liam Town</name><affiliation wicri:level="1"><nlm:affiliation>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland 4006</wicri:regionArea><wicri:noRegion>Queensland 4006</wicri:noRegion></affiliation></author><author><name sortKey="Huntington, Nicholas D" sort="Huntington, Nicholas D" uniqKey="Huntington N" first="Nicholas D" last="Huntington">Nicholas D. Huntington</name><affiliation wicri:level="4"><nlm:affiliation>The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Bartholin, Laurent" sort="Bartholin, Laurent" uniqKey="Bartholin L" first="Laurent" last="Bartholin">Laurent Bartholin</name><affiliation wicri:level="1"><nlm:affiliation>Immunology Virology and Inflammation Department, INSERM U1052, CNRS 5286 Centre de Recherche en Cancérologie de Lyon, 69008 Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Immunology Virology and Inflammation Department, INSERM U1052, CNRS 5286 Centre de Recherche en Cancérologie de Lyon, 69008 Lyon</wicri:regionArea><wicri:noRegion>69008 Lyon</wicri:noRegion><placeName><settlement type="city">Lyon</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Finlay, David" sort="Finlay, David" uniqKey="Finlay D" first="David" last="Finlay">David Finlay</name><affiliation wicri:level="1"><nlm:affiliation>School of Biochemistry and Immunology and School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.</nlm:affiliation><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>School of Biochemistry and Immunology and School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2</wicri:regionArea><wicri:noRegion>Dublin 2</wicri:noRegion></affiliation></author><author><name sortKey="Smyth, Mark J" sort="Smyth, Mark J" uniqKey="Smyth M" first="Mark J" last="Smyth">Mark J. Smyth</name><affiliation wicri:level="1"><nlm:affiliation>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia. School of Medicine, The University of Queensland, Herston, Queensland 4006, Australia. mark.smyth@qimrberghofer.edu.au thierry.walzer@inserm.fr.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia. School of Medicine, The University of Queensland, Herston, Queensland 4006</wicri:regionArea><wicri:noRegion>Queensland 4006</wicri:noRegion></affiliation></author><author><name sortKey="Walzer, Thierry" sort="Walzer, Thierry" uniqKey="Walzer T" first="Thierry" last="Walzer">Thierry Walzer</name><affiliation wicri:level="1"><nlm:affiliation>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon, France. mark.smyth@qimrberghofer.edu.au thierry.walzer@inserm.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre International de Recherche en Infectiologie (CIRI), 69007 Lyon, France. INSERM U1111, 69007 Lyon, France. Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Université Lyon 1, 69007 Lyon, France. CNRS, UMR5308, 69007 Lyon</wicri:regionArea><wicri:noRegion>69007 Lyon</wicri:noRegion><placeName><settlement type="city">Lyon</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author></analytic><series><title level="j">Science signaling</title><idno type="eISSN">1937-9145</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Humans</term><term>Immunity, Cellular</term><term>Interleukin-15 (immunology)</term><term>Killer Cells, Natural (immunology)</term><term>Killer Cells, Natural (pathology)</term><term>Lymphocyte Activation</term><term>Mice</term><term>Mice, Knockout</term><term>Neoplasms, Experimental (genetics)</term><term>Neoplasms, Experimental (immunology)</term><term>Signal Transduction (immunology)</term><term>TOR Serine-Threonine Kinases (genetics)</term><term>TOR Serine-Threonine Kinases (immunology)</term><term>Transforming Growth Factor beta (genetics)</term><term>Transforming Growth Factor beta (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Activation des lymphocytes</term><term>Animaux</term><term>Cellules tueuses naturelles (anatomopathologie)</term><term>Cellules tueuses naturelles (immunologie)</term><term>Facteur de croissance transformant bêta (génétique)</term><term>Facteur de croissance transformant bêta (immunologie)</term><term>Humains</term><term>Immunité cellulaire</term><term>Interleukine-15 (immunologie)</term><term>Souris</term><term>Souris knockout</term><term>Sérine-thréonine kinases TOR (génétique)</term><term>Sérine-thréonine kinases TOR (immunologie)</term><term>Transduction du signal (immunologie)</term><term>Tumeurs expérimentales (génétique)</term><term>Tumeurs expérimentales (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>TOR Serine-Threonine Kinases</term><term>Transforming Growth Factor beta</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Interleukin-15</term><term>TOR Serine-Threonine Kinases</term><term>Transforming Growth Factor beta</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Cellules tueuses naturelles</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Neoplasms, Experimental</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteur de croissance transformant bêta</term><term>Sérine-thréonine kinases TOR</term><term>Tumeurs expérimentales</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Cellules tueuses naturelles</term><term>Facteur de croissance transformant bêta</term><term>Interleukine-15</term><term>Sérine-thréonine kinases TOR</term><term>Transduction du signal</term><term>Tumeurs expérimentales</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Killer Cells, Natural</term><term>Neoplasms, Experimental</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Killer Cells, Natural</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Humans</term><term>Immunity, Cellular</term><term>Lymphocyte Activation</term><term>Mice</term><term>Mice, Knockout</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Activation des lymphocytes</term><term>Animaux</term><term>Humains</term><term>Immunité cellulaire</term><term>Souris</term><term>Souris knockout</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Transforming growth factor-β (TGF-β) is a major immunosuppressive cytokine that maintains immune homeostasis and prevents autoimmunity through its antiproliferative and anti-inflammatory properties in various immune cell types. We provide genetic, pharmacologic, and biochemical evidence that a critical target of TGF-β signaling in mouse and human natural killer (NK) cells is the serine and threonine kinase mTOR (mammalian target of rapamycin). Treatment of mouse or human NK cells with TGF-β in vitro blocked interleukin-15 (IL-15)-induced activation of mTOR. TGF-β and the mTOR inhibitor rapamycin both reduced the metabolic activity and proliferation of NK cells and reduced the abundances of various NK cell receptors and the cytotoxic activity of NK cells. In vivo, constitutive TGF-β signaling or depletion of mTOR arrested NK cell development, whereas deletion of the TGF-β receptor subunit TGF-βRII enhanced mTOR activity and the cytotoxic activity of the NK cells in response to IL-15. Suppression of TGF-β signaling in NK cells did not affect either NK cell development or homeostasis; however, it enhanced the ability of NK cells to limit metastases in two different tumor models in mice. Together, these results suggest that the kinase mTOR is a crucial signaling integrator of pro- and anti-inflammatory cytokines in NK cells. Moreover, we propose that boosting the metabolic activity of antitumor lymphocytes could be an effective strategy to promote immune-mediated tumor suppression.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>France</li><li>Irlande (pays)</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Bade-Wurtemberg</li><li>District de Karlsruhe</li><li>Rhône-Alpes</li><li>Victoria (État)</li></region><settlement><li>Heidelberg</li><li>Lyon</li><li>Melbourne</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Viel, Sebastien" sort="Viel, Sebastien" uniqKey="Viel S" first="Sébastien" last="Viel">Sébastien Viel</name></region><name sortKey="Bartholin, Laurent" sort="Bartholin, Laurent" uniqKey="Bartholin L" first="Laurent" last="Bartholin">Laurent Bartholin</name><name sortKey="Bienvenu, Jacques" sort="Bienvenu, Jacques" uniqKey="Bienvenu J" first="Jacques" last="Bienvenu">Jacques Bienvenu</name><name sortKey="Caux, Christophe" sort="Caux, Christophe" uniqKey="Caux C" first="Christophe" last="Caux">Christophe Caux</name><name sortKey="Charrier, Emily" sort="Charrier, Emily" uniqKey="Charrier E" first="Emily" last="Charrier">Emily Charrier</name><name sortKey="Degouve, Sophie" sort="Degouve, Sophie" uniqKey="Degouve S" first="Sophie" last="Degouve">Sophie Degouve</name><name sortKey="Djebali, Sophia" sort="Djebali, Sophia" uniqKey="Djebali S" first="Sophia" last="Djebali">Sophia Djebali</name><name sortKey="Grau, Morgan" sort="Grau, Morgan" uniqKey="Grau M" first="Morgan" last="Grau">Morgan Grau</name><name sortKey="Marcais, Antoine" sort="Marcais, Antoine" uniqKey="Marcais A" first="Antoine" last="Marçais">Antoine Marçais</name><name sortKey="Marvel, Jacqueline" sort="Marvel, Jacqueline" uniqKey="Marvel J" first="Jacqueline" last="Marvel">Jacqueline Marvel</name><name sortKey="Rabilloud, Jessica" sort="Rabilloud, Jessica" uniqKey="Rabilloud J" first="Jessica" last="Rabilloud">Jessica Rabilloud</name><name sortKey="Sanlaville, Amelien" sort="Sanlaville, Amelien" uniqKey="Sanlaville A" first="Amélien" last="Sanlaville">Amélien Sanlaville</name><name sortKey="Walzer, Thierry" sort="Walzer, Thierry" uniqKey="Walzer T" first="Thierry" last="Walzer">Thierry Walzer</name></country><country name="Australie"><noRegion><name sortKey="Guimaraes, Fernando Souza Fonseca" sort="Guimaraes, Fernando Souza Fonseca" uniqKey="Guimaraes F" first="Fernando Souza-Fonseca" last="Guimaraes">Fernando Souza-Fonseca Guimaraes</name></noRegion><name sortKey="Huntington, Nicholas D" sort="Huntington, Nicholas D" uniqKey="Huntington N" first="Nicholas D" last="Huntington">Nicholas D. Huntington</name><name sortKey="Smyth, Mark J" sort="Smyth, Mark J" uniqKey="Smyth M" first="Mark J" last="Smyth">Mark J. Smyth</name><name sortKey="Town, Liam" sort="Town, Liam" uniqKey="Town L" first="Liam" last="Town">Liam Town</name></country><country name="Irlande (pays)"><noRegion><name sortKey="Loftus, Roisin" sort="Loftus, Roisin" uniqKey="Loftus R" first="Roisin" last="Loftus">Roisin Loftus</name></noRegion><name sortKey="Finlay, David" sort="Finlay, David" uniqKey="Finlay D" first="David" last="Finlay">David Finlay</name></country><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Marie, Julien C" sort="Marie, Julien C" uniqKey="Marie J" first="Julien C" last="Marie">Julien C. Marie</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|area= AustralieFrV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:26884601
|texte= TGF-β inhibits the activation and functions of NK cells by repressing the mTOR pathway.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:26884601" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a AustralieFrV1
| This area was generated with Dilib version V0.6.33. |  |