Sex Differences in Plasmacytoid Dendritic Cell Levels of IRF5 Drive Higher IFN-α Production in Women
Identifieur interne : 002843 ( Main/Exploration ); précédent : 002842; suivant : 002844Sex Differences in Plasmacytoid Dendritic Cell Levels of IRF5 Drive Higher IFN-α Production in Women
Auteurs : Morgane Griesbeck [États-Unis, France] ; Susanne Ziegler [Allemagne] ; Sophie Laffont [France] ; Nikaïa Smith [France] ; Lise Chauveau [France] ; Phillip Tomezsko [États-Unis] ; Armon Sharei [États-Unis] ; Georgio Kourjian [États-Unis] ; Filippos Porichis [États-Unis] ; Meghan Hart [États-Unis] ; Christine D. Palmer [États-Unis] ; Michael Sirignano [États-Unis] ; Claudia Beisel [Allemagne] ; Heike Hildebrandt [Allemagne] ; Claire Cénac [France] ; Alexandra-Chloé Villani [États-Unis] ; Thomas J. Diefenbach [États-Unis] ; Sylvie Le Gall [États-Unis] ; Olivier Schwartz [France] ; Jean-Philippe Herbeuval [France] ; Brigitte Autran [France] ; Jean-Charles Guéry [France] ; J. Judy Chang [États-Unis, Australie] ; Marcus Altfeld [États-Unis, Allemagne]Source :
- The Journal of Immunology Author Choice [ 0022-1767 ] ; 2015.
Descripteurs français
- KwdFr :
- ARN messager (biosynthèse), Animaux, Caractères sexuels, Cellules cultivées, Cellules dendritiques (immunologie), Facteurs de régulation d'interféron (génétique), Facteurs de régulation d'interféron (métabolisme), Facteurs de régulation d'interféron (pharmacologie), Femelle, Humains, Interféron alpha (biosynthèse), Interféron alpha (sécrétion), Mâle, Protéines recombinantes (pharmacologie), Récepteur alpha des oestrogènes (génétique), Récepteur de type Toll-7 (métabolisme), Régulation de l'expression des gènes, Souris, Souris transgéniques, Transduction du signal (génétique).
- MESH :
- biosynthèse : ARN messager, Interféron alpha.
- génétique : Facteurs de régulation d'interféron, Récepteur alpha des oestrogènes, Transduction du signal.
- immunologie : Cellules dendritiques.
- métabolisme : Facteurs de régulation d'interféron, Récepteur de type Toll-7.
- pharmacologie : Facteurs de régulation d'interféron, Protéines recombinantes.
- sécrétion : Interféron alpha.
- Animaux, Caractères sexuels, Cellules cultivées, Femelle, Humains, Mâle, Régulation de l'expression des gènes, Souris, Souris transgéniques.
English descriptors
- KwdEn :
- Animals, Cells, Cultured, Dendritic Cells (immunology), Estrogen Receptor alpha (genetics), Female, Gene Expression Regulation, Humans, Interferon Regulatory Factors (genetics), Interferon Regulatory Factors (metabolism), Interferon Regulatory Factors (pharmacology), Interferon-alpha (biosynthesis), Interferon-alpha (secretion), Male, Mice, Mice, Transgenic, RNA, Messenger (biosynthesis), Recombinant Proteins (pharmacology), Sex Characteristics, Signal Transduction (genetics), Toll-Like Receptor 7 (metabolism).
- MESH :
- chemical , biosynthesis : Interferon-alpha, RNA, Messenger.
- chemical , genetics : Estrogen Receptor alpha, Interferon Regulatory Factors.
- genetics : Signal Transduction.
- immunology : Dendritic Cells.
- chemical , metabolism : Interferon Regulatory Factors, Toll-Like Receptor 7.
- chemical , pharmacology : Interferon Regulatory Factors, Recombinant Proteins.
- chemical , secretion : Interferon-alpha.
- Animals, Cells, Cultured, Female, Gene Expression Regulation, Humans, Male, Mice, Mice, Transgenic, Sex Characteristics.
Abstract
Increased IFN-α production contributes to the pathogenesis of infectious and autoimmune diseases. Plasmacytoid dendritic cells (pDCs) from females produce more IFN-α upon TLR7 stimulation than pDCs from males, yet the mechanisms underlying this difference remain unclear. In this article, we show that basal levels of IFN regulatory factor (IRF) 5 in pDCs were significantly higher in females compared with males and positively correlated with the percentage of IFN-α–secreting pDCs. Delivery of recombinant IRF5 protein into human primary pDCs increased TLR7-mediated IFN-α secretion. In mice, genetic ablation of the estrogen receptor 1 (
Url:
DOI: 10.4049/jimmunol.1501684
PubMed: 26519527
PubMed Central: 4654231
Affiliations:
- Allemagne, Australie, France, États-Unis
- Hambourg, Massachusetts, Midi-Pyrénées, Occitanie (région administrative), Île-de-France
- Hambourg, Paris, Toulouse
- Université Paris-Descartes
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Le document en format XML
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Judy" last="Chang">J. Judy Chang</name><affiliation wicri:level="2"><nlm:aff id="aff1">Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Ragon Institute of MGH, MIT and Harvard, Cambridge</wicri:cityArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff12">Department of Infectious Diseases, Monash University, Melbourne, Victoria 3800, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Infectious Diseases, Monash University, Melbourne, Victoria 3800</wicri:regionArea><wicri:noRegion>Victoria 3800</wicri:noRegion></affiliation></author><author><name sortKey="Altfeld, Marcus" sort="Altfeld, Marcus" uniqKey="Altfeld M" first="Marcus" last="Altfeld">Marcus Altfeld</name><affiliation wicri:level="2"><nlm:aff id="aff1">Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;</nlm:aff><country 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Cambridge</wicri:cityArea></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2">Centre d'Immunonologie et des Maladies Infectieuses-Paris, Université Pierre et Marie Curie/INSERM U1135, Hôpital Pitié Salpêtrière, Paris 75013, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre d'Immunonologie et des Maladies Infectieuses-Paris, Université Pierre et Marie Curie/INSERM U1135, Hôpital Pitié Salpêtrière, Paris 75013</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Ziegler, Susanne" sort="Ziegler, Susanne" uniqKey="Ziegler S" first="Susanne" last="Ziegler">Susanne Ziegler</name><affiliation wicri:level="1"><nlm:aff id="aff3">Heinrich Pette Institute-Leibniz Institute for Experimental Virology, Hamburg 20246, Germany;</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Heinrich Pette Institute-Leibniz Institute for Experimental Virology, Hamburg 20246</wicri:regionArea><wicri:noRegion>20246</wicri:noRegion><placeName><settlement type="city">Hambourg</settlement><region type="land" nuts="2">Hambourg</region></placeName></affiliation></author><author><name sortKey="Laffont, Sophie" sort="Laffont, Sophie" uniqKey="Laffont S" first="Sophie" last="Laffont">Sophie Laffont</name><affiliation wicri:level="1"><nlm:aff id="aff4">INSERM U1043, Toulouse F-31300, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1043, Toulouse F-31300</wicri:regionArea><wicri:noRegion>31300</wicri:noRegion><placeName><settlement type="city">Toulouse</settlement><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">CNRS, U5282, Toulouse F-31300, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CNRS, U5282, Toulouse F-31300</wicri:regionArea><wicri:noRegion>31300</wicri:noRegion><placeName><settlement type="city">Toulouse</settlement><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6">Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse F-31300, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse F-31300</wicri:regionArea><wicri:noRegion>31300</wicri:noRegion><placeName><settlement type="city">Toulouse</settlement><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region></placeName></affiliation></author><author><name sortKey="Smith, Nikaia" sort="Smith, Nikaia" uniqKey="Smith N" first="Nikaïa" last="Smith">Nikaïa Smith</name><affiliation wicri:level="4"><nlm:aff id="aff7">Chemistry and Biology, Nucleotides and Immunology for Therapy, CNRS UMR-8601, Université Paris Descartes, Paris 75270, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Chemistry and Biology, Nucleotides and Immunology for Therapy, CNRS UMR-8601, Université Paris Descartes, Paris 75270</wicri:regionArea><wicri:noRegion>75270</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author><author><name sortKey="Chauveau, Lise" sort="Chauveau, Lise" uniqKey="Chauveau L" first="Lise" last="Chauveau">Lise Chauveau</name><affiliation wicri:level="1"><nlm:aff id="aff8">Institut Pasteur, Unité de recherche associée CNRS 3015, Unite Virus et Immunité, Paris 75015, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur, Unité de recherche associée CNRS 3015, Unite Virus et Immunité, Paris 75015</wicri:regionArea><wicri:noRegion>75015</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Tomezsko, Phillip" sort="Tomezsko, Phillip" uniqKey="Tomezsko P" first="Phillip" last="Tomezsko">Phillip Tomezsko</name><affiliation wicri:level="2"><nlm:aff id="aff1">Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Ragon Institute of MGH, MIT and Harvard, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Sharei, Armon" sort="Sharei, Armon" uniqKey="Sharei A" first="Armon" last="Sharei">Armon Sharei</name><affiliation wicri:level="2"><nlm:aff id="aff9">The David H. Koch Institute for Integrative Cancer Research, Cambridge, MA 02139;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>The David H. Koch Institute for Integrative Cancer Research, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Kourjian, Georgio" sort="Kourjian, Georgio" uniqKey="Kourjian G" first="Georgio" last="Kourjian">Georgio Kourjian</name><affiliation wicri:level="2"><nlm:aff id="aff1">Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Ragon Institute of MGH, MIT and Harvard, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Porichis, Filippos" sort="Porichis, Filippos" uniqKey="Porichis F" first="Filippos" last="Porichis">Filippos Porichis</name><affiliation wicri:level="2"><nlm:aff id="aff1">Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Ragon Institute of MGH, MIT and Harvard, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Hart, Meghan" sort="Hart, Meghan" uniqKey="Hart M" first="Meghan" last="Hart">Meghan Hart</name><affiliation wicri:level="2"><nlm:aff id="aff1">Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Ragon Institute of MGH, MIT and Harvard, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Palmer, Christine D" sort="Palmer, Christine D" uniqKey="Palmer C" first="Christine D." last="Palmer">Christine D. Palmer</name><affiliation wicri:level="2"><nlm:aff id="aff1">Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Ragon Institute of MGH, MIT and Harvard, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Sirignano, Michael" sort="Sirignano, Michael" uniqKey="Sirignano M" first="Michael" last="Sirignano">Michael Sirignano</name><affiliation wicri:level="2"><nlm:aff id="aff1">Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Ragon Institute of MGH, MIT and Harvard, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Beisel, Claudia" sort="Beisel, Claudia" uniqKey="Beisel C" first="Claudia" last="Beisel">Claudia Beisel</name><affiliation wicri:level="1"><nlm:aff id="aff3">Heinrich Pette Institute-Leibniz Institute for Experimental Virology, Hamburg 20246, Germany;</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Heinrich Pette Institute-Leibniz Institute for Experimental Virology, Hamburg 20246</wicri:regionArea><wicri:noRegion>20246</wicri:noRegion><placeName><settlement type="city">Hambourg</settlement><region type="land" nuts="2">Hambourg</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff10">Medical Department, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany;</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Medical Department, University Hospital Hamburg-Eppendorf, Hamburg 20246</wicri:regionArea><wicri:noRegion>20246</wicri:noRegion><placeName><settlement type="city">Hambourg</settlement><region type="land" nuts="2">Hambourg</region></placeName></affiliation></author><author><name sortKey="Hildebrandt, Heike" sort="Hildebrandt, Heike" uniqKey="Hildebrandt H" first="Heike" last="Hildebrandt">Heike Hildebrandt</name><affiliation wicri:level="1"><nlm:aff id="aff3">Heinrich Pette Institute-Leibniz Institute for Experimental Virology, Hamburg 20246, Germany;</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Heinrich Pette Institute-Leibniz Institute for Experimental Virology, Hamburg 20246</wicri:regionArea><wicri:noRegion>20246</wicri:noRegion><placeName><settlement type="city">Hambourg</settlement><region type="land" nuts="2">Hambourg</region></placeName></affiliation></author><author><name sortKey="Cenac, Claire" sort="Cenac, Claire" uniqKey="Cenac C" first="Claire" last="Cénac">Claire Cénac</name><affiliation wicri:level="1"><nlm:aff id="aff4">INSERM U1043, Toulouse F-31300, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1043, Toulouse F-31300</wicri:regionArea><wicri:noRegion>31300</wicri:noRegion><placeName><settlement type="city">Toulouse</settlement><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">CNRS, U5282, Toulouse F-31300, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CNRS, U5282, Toulouse F-31300</wicri:regionArea><wicri:noRegion>31300</wicri:noRegion><placeName><settlement type="city">Toulouse</settlement><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6">Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse F-31300, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse F-31300</wicri:regionArea><wicri:noRegion>31300</wicri:noRegion><placeName><settlement type="city">Toulouse</settlement><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region></placeName></affiliation></author><author><name sortKey="Villani, Alexandra Chloe" sort="Villani, Alexandra Chloe" uniqKey="Villani A" first="Alexandra-Chloé" last="Villani">Alexandra-Chloé Villani</name><affiliation wicri:level="2"><nlm:aff wicri:cut="; and" id="aff11">Broad Institute of MIT and Harvard, Cambridge, MA 02139</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Broad Institute of MIT and Harvard, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Diefenbach, Thomas J" sort="Diefenbach, Thomas J" uniqKey="Diefenbach T" first="Thomas J." last="Diefenbach">Thomas J. Diefenbach</name><affiliation wicri:level="2"><nlm:aff id="aff1">Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Ragon Institute of MGH, MIT and Harvard, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Le Gall, Sylvie" sort="Le Gall, Sylvie" uniqKey="Le Gall S" first="Sylvie" last="Le Gall">Sylvie Le Gall</name><affiliation wicri:level="2"><nlm:aff id="aff1">Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Ragon Institute of MGH, MIT and Harvard, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Schwartz, Olivier" sort="Schwartz, Olivier" uniqKey="Schwartz O" first="Olivier" last="Schwartz">Olivier Schwartz</name><affiliation wicri:level="1"><nlm:aff id="aff8">Institut Pasteur, Unité de recherche associée CNRS 3015, Unite Virus et Immunité, Paris 75015, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur, Unité de recherche associée CNRS 3015, Unite Virus et Immunité, Paris 75015</wicri:regionArea><wicri:noRegion>75015</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Herbeuval, Jean Philippe" sort="Herbeuval, Jean Philippe" uniqKey="Herbeuval J" first="Jean-Philippe" last="Herbeuval">Jean-Philippe Herbeuval</name><affiliation wicri:level="4"><nlm:aff id="aff7">Chemistry and Biology, Nucleotides and Immunology for Therapy, CNRS UMR-8601, Université Paris Descartes, Paris 75270, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Chemistry and Biology, Nucleotides and Immunology for Therapy, CNRS UMR-8601, Université Paris Descartes, Paris 75270</wicri:regionArea><wicri:noRegion>75270</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author><author><name sortKey="Autran, Brigitte" sort="Autran, Brigitte" uniqKey="Autran B" first="Brigitte" last="Autran">Brigitte Autran</name><affiliation wicri:level="1"><nlm:aff id="aff2">Centre d'Immunonologie et des Maladies Infectieuses-Paris, Université Pierre et Marie Curie/INSERM U1135, Hôpital Pitié Salpêtrière, Paris 75013, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre d'Immunonologie et des Maladies Infectieuses-Paris, Université Pierre et Marie Curie/INSERM U1135, Hôpital Pitié Salpêtrière, Paris 75013</wicri:regionArea><wicri:noRegion>75013</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Guery, Jean Charles" sort="Guery, Jean Charles" uniqKey="Guery J" first="Jean-Charles" last="Guéry">Jean-Charles Guéry</name><affiliation wicri:level="1"><nlm:aff id="aff4">INSERM U1043, Toulouse F-31300, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1043, Toulouse F-31300</wicri:regionArea><wicri:noRegion>31300</wicri:noRegion><placeName><settlement type="city">Toulouse</settlement><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">CNRS, U5282, Toulouse F-31300, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CNRS, U5282, Toulouse F-31300</wicri:regionArea><wicri:noRegion>31300</wicri:noRegion><placeName><settlement type="city">Toulouse</settlement><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6">Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse F-31300, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse F-31300</wicri:regionArea><wicri:noRegion>31300</wicri:noRegion><placeName><settlement type="city">Toulouse</settlement><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region></placeName></affiliation></author><author><name sortKey="Chang, J Judy" sort="Chang, J Judy" uniqKey="Chang J" first="J. Judy" last="Chang">J. Judy Chang</name><affiliation wicri:level="2"><nlm:aff id="aff1">Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Ragon Institute of MGH, MIT and Harvard, Cambridge</wicri:cityArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff12">Department of Infectious Diseases, Monash University, Melbourne, Victoria 3800, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Infectious Diseases, Monash University, Melbourne, Victoria 3800</wicri:regionArea><wicri:noRegion>Victoria 3800</wicri:noRegion></affiliation></author><author><name sortKey="Altfeld, Marcus" sort="Altfeld, Marcus" uniqKey="Altfeld M" first="Marcus" last="Altfeld">Marcus Altfeld</name><affiliation wicri:level="2"><nlm:aff id="aff1">Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Ragon Institute of MGH, MIT and Harvard, Cambridge</wicri:cityArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Heinrich Pette Institute-Leibniz Institute for Experimental Virology, Hamburg 20246, Germany;</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Heinrich Pette Institute-Leibniz Institute for Experimental Virology, Hamburg 20246</wicri:regionArea><wicri:noRegion>20246</wicri:noRegion><placeName><settlement type="city">Hambourg</settlement><region type="land" nuts="2">Hambourg</region></placeName></affiliation></author></analytic><series><title level="j">The Journal of Immunology Author Choice</title><idno type="ISSN">0022-1767</idno><idno type="eISSN">1550-6606</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" 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d'interféron (génétique)</term><term>Facteurs de régulation d'interféron (métabolisme)</term><term>Facteurs de régulation d'interféron (pharmacologie)</term><term>Femelle</term><term>Humains</term><term>Interféron alpha (biosynthèse)</term><term>Interféron alpha (sécrétion)</term><term>Mâle</term><term>Protéines recombinantes (pharmacologie)</term><term>Récepteur alpha des oestrogènes (génétique)</term><term>Récepteur de type Toll-7 (métabolisme)</term><term>Régulation de l'expression des gènes</term><term>Souris</term><term>Souris transgéniques</term><term>Transduction du signal (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Interferon-alpha</term><term>RNA, Messenger</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Estrogen Receptor alpha</term><term>Interferon Regulatory Factors</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>ARN messager</term><term>Interféron alpha</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteurs de régulation d'interféron</term><term>Récepteur alpha des oestrogènes</term><term>Transduction du signal</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Cellules dendritiques</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Dendritic Cells</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Interferon Regulatory Factors</term><term>Toll-Like Receptor 7</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteurs de régulation d'interféron</term><term>Récepteur de type Toll-7</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Facteurs de régulation d'interféron</term><term>Protéines recombinantes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Interferon Regulatory Factors</term><term>Recombinant Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="secretion" xml:lang="en"><term>Interferon-alpha</term></keywords><keywords scheme="MESH" qualifier="sécrétion" xml:lang="fr"><term>Interféron alpha</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cells, Cultured</term><term>Female</term><term>Gene Expression Regulation</term><term>Humans</term><term>Male</term><term>Mice</term><term>Mice, Transgenic</term><term>Sex Characteristics</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Caractères sexuels</term><term>Cellules cultivées</term><term>Femelle</term><term>Humains</term><term>Mâle</term><term>Régulation de l'expression des gènes</term><term>Souris</term><term>Souris transgéniques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Increased IFN-α production contributes to the pathogenesis of infectious and autoimmune diseases. Plasmacytoid dendritic cells (pDCs) from females produce more IFN-α upon TLR7 stimulation than pDCs from males, yet the mechanisms underlying this difference remain unclear. In this article, we show that basal levels of IFN regulatory factor (IRF) 5 in pDCs were significantly higher in females compared with males and positively correlated with the percentage of IFN-α–secreting pDCs. Delivery of recombinant IRF5 protein into human primary pDCs increased TLR7-mediated IFN-α secretion. In mice, genetic ablation of the estrogen receptor 1 (<italic>Esr1</italic>) gene in the hematopoietic compartment or DC lineage reduced <italic>Irf5</italic> mRNA expression in pDCs and IFN-α production. <italic>IRF5</italic> mRNA levels furthermore correlated with <italic>ESR1</italic> mRNA levels in human pDCs, consistent with <italic>IRF5</italic> regulation at the transcriptional level by <italic>ESR1</italic>. Taken together, these data demonstrate a critical mechanism by which sex differences in basal pDC IRF5 expression lead to higher IFN-α production upon TLR7 stimulation in females and provide novel targets for the modulation of immune responses and inflammation.</p></div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>France</li><li>États-Unis</li></country><region><li>Hambourg</li><li>Massachusetts</li><li>Midi-Pyrénées</li><li>Occitanie (région administrative)</li><li>Île-de-France</li></region><settlement><li>Hambourg</li><li>Paris</li><li>Toulouse</li></settlement><orgName><li>Université Paris-Descartes</li></orgName></list><tree><country name="États-Unis"><region name="Massachusetts"><name sortKey="Griesbeck, Morgane" sort="Griesbeck, Morgane" uniqKey="Griesbeck M" first="Morgane" last="Griesbeck">Morgane Griesbeck</name></region><name sortKey="Altfeld, Marcus" sort="Altfeld, Marcus" uniqKey="Altfeld M" first="Marcus" last="Altfeld">Marcus Altfeld</name><name sortKey="Chang, J Judy" sort="Chang, J Judy" uniqKey="Chang J" first="J. Judy" last="Chang">J. Judy Chang</name><name sortKey="Diefenbach, Thomas J" sort="Diefenbach, Thomas J" uniqKey="Diefenbach T" first="Thomas J." last="Diefenbach">Thomas J. Diefenbach</name><name sortKey="Hart, Meghan" sort="Hart, Meghan" uniqKey="Hart M" first="Meghan" last="Hart">Meghan Hart</name><name sortKey="Kourjian, Georgio" sort="Kourjian, Georgio" uniqKey="Kourjian G" first="Georgio" last="Kourjian">Georgio Kourjian</name><name sortKey="Le Gall, Sylvie" sort="Le Gall, Sylvie" uniqKey="Le Gall S" first="Sylvie" last="Le Gall">Sylvie Le Gall</name><name sortKey="Palmer, Christine D" sort="Palmer, Christine D" uniqKey="Palmer C" first="Christine D." last="Palmer">Christine D. Palmer</name><name sortKey="Porichis, Filippos" sort="Porichis, Filippos" uniqKey="Porichis F" first="Filippos" last="Porichis">Filippos Porichis</name><name sortKey="Sharei, Armon" sort="Sharei, Armon" uniqKey="Sharei A" first="Armon" last="Sharei">Armon Sharei</name><name sortKey="Sirignano, Michael" sort="Sirignano, Michael" uniqKey="Sirignano M" first="Michael" last="Sirignano">Michael Sirignano</name><name sortKey="Tomezsko, Phillip" sort="Tomezsko, Phillip" uniqKey="Tomezsko P" first="Phillip" last="Tomezsko">Phillip Tomezsko</name><name sortKey="Villani, Alexandra Chloe" sort="Villani, Alexandra Chloe" uniqKey="Villani A" first="Alexandra-Chloé" last="Villani">Alexandra-Chloé Villani</name></country><country name="France"><region name="Île-de-France"><name sortKey="Griesbeck, Morgane" sort="Griesbeck, Morgane" uniqKey="Griesbeck M" first="Morgane" last="Griesbeck">Morgane Griesbeck</name></region><name sortKey="Autran, Brigitte" sort="Autran, Brigitte" uniqKey="Autran B" first="Brigitte" last="Autran">Brigitte Autran</name><name sortKey="Cenac, Claire" sort="Cenac, Claire" uniqKey="Cenac C" first="Claire" last="Cénac">Claire Cénac</name><name sortKey="Cenac, Claire" sort="Cenac, Claire" uniqKey="Cenac C" first="Claire" last="Cénac">Claire Cénac</name><name sortKey="Cenac, Claire" sort="Cenac, Claire" uniqKey="Cenac C" first="Claire" last="Cénac">Claire Cénac</name><name sortKey="Chauveau, Lise" sort="Chauveau, Lise" uniqKey="Chauveau L" first="Lise" last="Chauveau">Lise Chauveau</name><name sortKey="Guery, Jean Charles" sort="Guery, Jean Charles" uniqKey="Guery J" first="Jean-Charles" last="Guéry">Jean-Charles Guéry</name><name sortKey="Guery, Jean Charles" sort="Guery, Jean Charles" uniqKey="Guery J" first="Jean-Charles" last="Guéry">Jean-Charles Guéry</name><name sortKey="Guery, Jean Charles" sort="Guery, Jean Charles" uniqKey="Guery J" first="Jean-Charles" last="Guéry">Jean-Charles Guéry</name><name sortKey="Herbeuval, Jean Philippe" sort="Herbeuval, Jean Philippe" uniqKey="Herbeuval J" first="Jean-Philippe" last="Herbeuval">Jean-Philippe Herbeuval</name><name sortKey="Laffont, Sophie" sort="Laffont, Sophie" uniqKey="Laffont S" first="Sophie" last="Laffont">Sophie Laffont</name><name sortKey="Laffont, Sophie" sort="Laffont, Sophie" uniqKey="Laffont S" first="Sophie" last="Laffont">Sophie Laffont</name><name sortKey="Laffont, Sophie" sort="Laffont, Sophie" uniqKey="Laffont S" first="Sophie" last="Laffont">Sophie Laffont</name><name sortKey="Schwartz, Olivier" sort="Schwartz, Olivier" uniqKey="Schwartz O" first="Olivier" last="Schwartz">Olivier Schwartz</name><name sortKey="Smith, Nikaia" sort="Smith, Nikaia" uniqKey="Smith N" first="Nikaïa" last="Smith">Nikaïa Smith</name></country><country name="Allemagne"><region name="Hambourg"><name sortKey="Ziegler, Susanne" sort="Ziegler, Susanne" uniqKey="Ziegler S" first="Susanne" last="Ziegler">Susanne Ziegler</name></region><name sortKey="Altfeld, Marcus" sort="Altfeld, Marcus" uniqKey="Altfeld M" first="Marcus" last="Altfeld">Marcus Altfeld</name><name sortKey="Beisel, Claudia" sort="Beisel, Claudia" uniqKey="Beisel C" first="Claudia" last="Beisel">Claudia Beisel</name><name sortKey="Beisel, Claudia" sort="Beisel, Claudia" uniqKey="Beisel C" first="Claudia" last="Beisel">Claudia Beisel</name><name sortKey="Hildebrandt, Heike" sort="Hildebrandt, Heike" uniqKey="Hildebrandt H" first="Heike" last="Hildebrandt">Heike Hildebrandt</name></country><country name="Australie"><noRegion><name sortKey="Chang, J Judy" sort="Chang, J Judy" uniqKey="Chang J" first="J. Judy" last="Chang">J. Judy Chang</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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