Androgen signaling negatively controls group 2 innate lymphoid cells.
Identifieur interne : 001187 ( Main/Exploration ); précédent : 001186; suivant : 001188Androgen signaling negatively controls group 2 innate lymphoid cells.
Auteurs : Sophie Laffont [France] ; Eve Blanquart [France] ; Magali Savignac [France] ; Claire Cénac [France] ; Gilles Laverny [France] ; Daniel Metzger [France] ; Jean-Philippe Girard [France] ; Gabrielle T. Belz [Australie] ; Lucette Pelletier [France] ; Cyril Seillet [France] ; Jean-Charles Guéry [France]Source :
- The Journal of experimental medicine [ 1540-9538 ] ; 2017.
Descripteurs français
- KwdFr :
- Androgènes (métabolisme), Androgènes (pharmacologie), Animaux, Asthme (), Asthme (anatomopathologie), Asthme (immunologie), Castration, Femelle, Hypersensibilité (), Hypersensibilité (anatomopathologie), Hypersensibilité (immunologie), Immunité innée (immunologie), Interleukine-33 (métabolisme), Lymphocytes (immunologie), Mâle, Numération des lymphocytes, Pneumopathie infectieuse (), Pneumopathie infectieuse (anatomopathologie), Pneumopathie infectieuse (immunologie), Poumon (anatomopathologie), Poumon (immunologie), Prolifération cellulaire (), Pyroglyphidae (immunologie), Récepteurs aux androgènes (métabolisme), Sexisme, Souris de lignée C57BL, Susceptibilité à une maladie, Transduction du signal.
- MESH :
- anatomopathologie : Asthme, Hypersensibilité, Pneumopathie infectieuse, Poumon.
- immunologie : Asthme, Hypersensibilité, Immunité innée, Lymphocytes, Pneumopathie infectieuse, Poumon, Pyroglyphidae.
- métabolisme : Androgènes, Interleukine-33, Récepteurs aux androgènes.
- pharmacologie : Androgènes.
- Animaux, Asthme, Castration, Femelle, Hypersensibilité, Mâle, Numération des lymphocytes, Pneumopathie infectieuse, Prolifération cellulaire, Sexisme, Souris de lignée C57BL, Susceptibilité à une maladie, Transduction du signal.
English descriptors
- KwdEn :
- Androgens (metabolism), Androgens (pharmacology), Animals, Asthma (complications), Asthma (immunology), Asthma (pathology), Castration, Cell Proliferation (drug effects), Disease Susceptibility, Female, Hypersensitivity (complications), Hypersensitivity (immunology), Hypersensitivity (pathology), Immunity, Innate (immunology), Interleukin-33 (metabolism), Lung (immunology), Lung (pathology), Lymphocyte Count, Lymphocytes (immunology), Male, Mice, Inbred C57BL, Pneumonia (complications), Pneumonia (immunology), Pneumonia (pathology), Pyroglyphidae (immunology), Receptors, Androgen (metabolism), Sexism, Signal Transduction.
- MESH :
- chemical , metabolism : Androgens, Interleukin-33, Receptors, Androgen.
- chemical , pharmacology : Androgens.
- complications : Asthma, Hypersensitivity, Pneumonia.
- drug effects : Cell Proliferation.
- immunology : Asthma, Hypersensitivity, Immunity, Innate, Lung, Lymphocytes, Pneumonia, Pyroglyphidae.
- pathology : Asthma, Hypersensitivity, Lung, Pneumonia.
- Animals, Castration, Disease Susceptibility, Female, Lymphocyte Count, Male, Mice, Inbred C57BL, Sexism, Signal Transduction.
Abstract
Prevalence of asthma is higher in women than in men, but the mechanisms underlying this sex bias are unknown. Group 2 innate lymphoid cells (ILC2s) are key regulators of type 2 inflammatory responses. Here, we show that ILC2 development is greatly influenced by male sex hormones. Male mice have reduced numbers of ILC2 progenitors (ILC2Ps) and mature ILC2s in peripheral tissues compared with females. In consequence, males exhibit reduced susceptibility to allergic airway inflammation in response to environmental allergens and less severe IL-33-driven lung inflammation, correlating with an impaired expansion of lung ILC2s. Importantly, orchiectomy, but not ovariectomy, abolishes the sex differences in ILC2 development and restores IL-33-mediated lung inflammation. ILC2Ps express the androgen receptor (AR), and AR signaling inhibits their differentiation into mature ILC2s. Finally, we show that hematopoietic AR expression limits IL-33-driven lung inflammation through a cell-intrinsic inhibition of ILC2 expansion. Thus, androgens play a crucial protective role in type 2 airway inflammation by negatively regulating ILC2 homeostasis, thereby limiting their capacity to expand locally in response to IL-33.
DOI: 10.1084/jem.20161807
PubMed: 28484078
Affiliations:
- Australie, France
- Alsace (région administrative), Grand Est, Midi-Pyrénées, Occitanie (région administrative), Victoria (État)
- Illkirch, Melbourne, Strasbourg, Toulouse
- Université de Melbourne, Université de Strasbourg
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Le document en format XML
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type="old region" nuts="2">Alsace (région administrative)</region></placeName></affiliation></author><author><name sortKey="Girard, Jean Philippe" sort="Girard, Jean Philippe" uniqKey="Girard J" first="Jean-Philippe" last="Girard">Jean-Philippe Girard</name><affiliation wicri:level="1"><nlm:affiliation>Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, 31077 Toulouse, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, 31077 Toulouse</wicri:regionArea><wicri:noRegion>31077 Toulouse</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="Belz, Gabrielle T" sort="Belz, Gabrielle T" uniqKey="Belz G" first="Gabrielle T" 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Belz</name><affiliation wicri:level="4"><nlm:affiliation>The Walter and Elisa Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>The Walter and Elisa Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria 3052</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="Pelletier, Lucette" sort="Pelletier, Lucette" uniqKey="Pelletier L" first="Lucette" last="Pelletier">Lucette Pelletier</name><affiliation wicri:level="1"><nlm:affiliation>Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Institut National de la Santé et de la Recherche Medicale (INSERM), Centre National de la Recherche Scientifique (CNRS), UPS, 31300 Toulouse, 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wicri:rule="url">France</country><wicri:regionArea>The Walter and Elisa Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion><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="Guery, Jean Charles" sort="Guery, Jean Charles" uniqKey="Guery J" first="Jean-Charles" last="Guéry">Jean-Charles Guéry</name><affiliation wicri:level="1"><nlm:affiliation>Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Institut National de la Santé et de la Recherche Medicale (INSERM), Centre National de la Recherche Scientifique (CNRS), UPS, 31300 Toulouse, France Jean-Charles.Guery@inserm.fr seillet@wehi.edu.au.</nlm:affiliation><country wicri:rule="url">France</country><wicri:regionArea>Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Institut National de la Santé et de la Recherche Medicale (INSERM), Centre National de la Recherche Scientifique (CNRS), UPS, 31300 Toulouse</wicri:regionArea><wicri:noRegion>31300 Toulouse</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></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28484078</idno><idno type="pmid">28484078</idno><idno type="doi">10.1084/jem.20161807</idno><idno type="wicri:Area/PubMed/Corpus">000B35</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000B35</idno><idno type="wicri:Area/PubMed/Curation">000B32</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000B32</idno><idno 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France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Institut National de la Santé et de la Recherche Medicale (INSERM), Centre National de la Recherche Scientifique (CNRS), UPS, 31300 Toulouse</wicri:regionArea><placeName><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Blanquart, Eve" sort="Blanquart, Eve" uniqKey="Blanquart E" first="Eve" last="Blanquart">Eve Blanquart</name><affiliation wicri:level="3"><nlm:affiliation>Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Institut National de la Santé et de la Recherche Medicale (INSERM), Centre National de la Recherche Scientifique (CNRS), UPS, 31300 Toulouse, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Institut National de la Santé et de la Recherche Medicale (INSERM), Centre National de la Recherche Scientifique (CNRS), UPS, 31300 Toulouse</wicri:regionArea><placeName><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Savignac, Magali" sort="Savignac, Magali" uniqKey="Savignac M" first="Magali" last="Savignac">Magali Savignac</name><affiliation wicri:level="3"><nlm:affiliation>Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Institut National de la Santé et de la Recherche Medicale (INSERM), Centre National de la Recherche Scientifique (CNRS), UPS, 31300 Toulouse, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Institut National de la Santé et de la Recherche Medicale (INSERM), Centre National de la Recherche Scientifique (CNRS), UPS, 31300 Toulouse</wicri:regionArea><placeName><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Cenac, Claire" sort="Cenac, Claire" uniqKey="Cenac C" first="Claire" last="Cénac">Claire Cénac</name><affiliation wicri:level="3"><nlm:affiliation>Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Institut National de la Santé et de la Recherche Medicale (INSERM), Centre National de la Recherche Scientifique (CNRS), UPS, 31300 Toulouse, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Institut National de la Santé et de la Recherche Medicale (INSERM), Centre National de la Recherche Scientifique (CNRS), UPS, 31300 Toulouse</wicri:regionArea><placeName><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Laverny, Gilles" sort="Laverny, Gilles" uniqKey="Laverny G" first="Gilles" last="Laverny">Gilles Laverny</name><affiliation wicri:level="4"><nlm:affiliation>Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Alsace (région administrative)</region><settlement type="city">Illkirch</settlement><settlement type="city">Strasbourg</settlement></placeName><orgName type="university">Université de Strasbourg</orgName></affiliation></author><author><name sortKey="Metzger, Daniel" sort="Metzger, Daniel" uniqKey="Metzger D" first="Daniel" last="Metzger">Daniel Metzger</name><affiliation wicri:level="4"><nlm:affiliation>Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch</wicri:regionArea><wicri:noRegion>67404 Illkirch</wicri:noRegion><orgName type="university">Université de Strasbourg</orgName><placeName><settlement type="city">Strasbourg</settlement><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Alsace (région administrative)</region></placeName></affiliation></author><author><name sortKey="Girard, Jean Philippe" sort="Girard, Jean Philippe" uniqKey="Girard J" first="Jean-Philippe" last="Girard">Jean-Philippe Girard</name><affiliation wicri:level="1"><nlm:affiliation>Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, 31077 Toulouse, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, 31077 Toulouse</wicri:regionArea><wicri:noRegion>31077 Toulouse</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="Belz, Gabrielle T" sort="Belz, Gabrielle T" uniqKey="Belz G" first="Gabrielle T" last="Belz">Gabrielle T. Belz</name><affiliation wicri:level="4"><nlm:affiliation>The Walter and Elisa Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>The Walter and Elisa Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria 3052</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="Pelletier, Lucette" sort="Pelletier, Lucette" uniqKey="Pelletier L" first="Lucette" last="Pelletier">Lucette Pelletier</name><affiliation wicri:level="1"><nlm:affiliation>Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Institut National de la Santé et de la Recherche Medicale (INSERM), Centre National de la Recherche Scientifique (CNRS), UPS, 31300 Toulouse, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Institut National de la Santé et de la Recherche Medicale (INSERM), Centre National de la Recherche Scientifique (CNRS), UPS, 31300 Toulouse</wicri:regionArea><wicri:noRegion>31300 Toulouse</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="Seillet, Cyril" sort="Seillet, Cyril" uniqKey="Seillet C" first="Cyril" last="Seillet">Cyril Seillet</name><affiliation wicri:level="4"><nlm:affiliation>The Walter and Elisa Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria 3052, Australia Jean-Charles.Guery@inserm.fr seillet@wehi.edu.au.</nlm:affiliation><country wicri:rule="url">France</country><wicri:regionArea>The Walter and Elisa Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion><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="Guery, Jean Charles" sort="Guery, Jean Charles" uniqKey="Guery J" first="Jean-Charles" last="Guéry">Jean-Charles Guéry</name><affiliation wicri:level="1"><nlm:affiliation>Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Institut National de la Santé et de la Recherche Medicale (INSERM), Centre National de la Recherche Scientifique (CNRS), UPS, 31300 Toulouse, France Jean-Charles.Guery@inserm.fr seillet@wehi.edu.au.</nlm:affiliation><country wicri:rule="url">France</country><wicri:regionArea>Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Institut National de la Santé et de la Recherche Medicale (INSERM), Centre National de la Recherche Scientifique (CNRS), UPS, 31300 Toulouse</wicri:regionArea><wicri:noRegion>31300 Toulouse</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></analytic><series><title level="j">The Journal of experimental medicine</title><idno type="eISSN">1540-9538</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Androgens (metabolism)</term><term>Androgens (pharmacology)</term><term>Animals</term><term>Asthma (complications)</term><term>Asthma (immunology)</term><term>Asthma (pathology)</term><term>Castration</term><term>Cell Proliferation (drug effects)</term><term>Disease Susceptibility</term><term>Female</term><term>Hypersensitivity (complications)</term><term>Hypersensitivity (immunology)</term><term>Hypersensitivity (pathology)</term><term>Immunity, Innate (immunology)</term><term>Interleukin-33 (metabolism)</term><term>Lung (immunology)</term><term>Lung (pathology)</term><term>Lymphocyte Count</term><term>Lymphocytes (immunology)</term><term>Male</term><term>Mice, Inbred C57BL</term><term>Pneumonia (complications)</term><term>Pneumonia (immunology)</term><term>Pneumonia (pathology)</term><term>Pyroglyphidae (immunology)</term><term>Receptors, Androgen (metabolism)</term><term>Sexism</term><term>Signal Transduction</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Androgènes (métabolisme)</term><term>Androgènes (pharmacologie)</term><term>Animaux</term><term>Asthme ()</term><term>Asthme (anatomopathologie)</term><term>Asthme (immunologie)</term><term>Castration</term><term>Femelle</term><term>Hypersensibilité ()</term><term>Hypersensibilité (anatomopathologie)</term><term>Hypersensibilité (immunologie)</term><term>Immunité innée (immunologie)</term><term>Interleukine-33 (métabolisme)</term><term>Lymphocytes (immunologie)</term><term>Mâle</term><term>Numération des lymphocytes</term><term>Pneumopathie infectieuse ()</term><term>Pneumopathie infectieuse (anatomopathologie)</term><term>Pneumopathie infectieuse (immunologie)</term><term>Poumon (anatomopathologie)</term><term>Poumon (immunologie)</term><term>Prolifération cellulaire ()</term><term>Pyroglyphidae (immunologie)</term><term>Récepteurs aux androgènes (métabolisme)</term><term>Sexisme</term><term>Souris de lignée C57BL</term><term>Susceptibilité à une maladie</term><term>Transduction du signal</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Androgens</term><term>Interleukin-33</term><term>Receptors, Androgen</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Androgens</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Asthme</term><term>Hypersensibilité</term><term>Pneumopathie infectieuse</term><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Asthma</term><term>Hypersensitivity</term><term>Pneumonia</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Proliferation</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Asthme</term><term>Hypersensibilité</term><term>Immunité innée</term><term>Lymphocytes</term><term>Pneumopathie infectieuse</term><term>Poumon</term><term>Pyroglyphidae</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Asthma</term><term>Hypersensitivity</term><term>Immunity, Innate</term><term>Lung</term><term>Lymphocytes</term><term>Pneumonia</term><term>Pyroglyphidae</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Androgènes</term><term>Interleukine-33</term><term>Récepteurs aux androgènes</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Asthma</term><term>Hypersensitivity</term><term>Lung</term><term>Pneumonia</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Androgènes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Castration</term><term>Disease Susceptibility</term><term>Female</term><term>Lymphocyte Count</term><term>Male</term><term>Mice, Inbred C57BL</term><term>Sexism</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Asthme</term><term>Castration</term><term>Femelle</term><term>Hypersensibilité</term><term>Mâle</term><term>Numération des lymphocytes</term><term>Pneumopathie infectieuse</term><term>Prolifération cellulaire</term><term>Sexisme</term><term>Souris de lignée C57BL</term><term>Susceptibilité à une maladie</term><term>Transduction du signal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Prevalence of asthma is higher in women than in men, but the mechanisms underlying this sex bias are unknown. Group 2 innate lymphoid cells (ILC2s) are key regulators of type 2 inflammatory responses. Here, we show that ILC2 development is greatly influenced by male sex hormones. Male mice have reduced numbers of ILC2 progenitors (ILC2Ps) and mature ILC2s in peripheral tissues compared with females. In consequence, males exhibit reduced susceptibility to allergic airway inflammation in response to environmental allergens and less severe IL-33-driven lung inflammation, correlating with an impaired expansion of lung ILC2s. Importantly, orchiectomy, but not ovariectomy, abolishes the sex differences in ILC2 development and restores IL-33-mediated lung inflammation. ILC2Ps express the androgen receptor (AR), and AR signaling inhibits their differentiation into mature ILC2s. Finally, we show that hematopoietic AR expression limits IL-33-driven lung inflammation through a cell-intrinsic inhibition of ILC2 expansion. Thus, androgens play a crucial protective role in type 2 airway inflammation by negatively regulating ILC2 homeostasis, thereby limiting their capacity to expand locally in response to IL-33.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Alsace (région administrative)</li><li>Grand Est</li><li>Midi-Pyrénées</li><li>Occitanie (région administrative)</li><li>Victoria (État)</li></region><settlement><li>Illkirch</li><li>Melbourne</li><li>Strasbourg</li><li>Toulouse</li></settlement><orgName><li>Université de Melbourne</li><li>Université de Strasbourg</li></orgName></list><tree><country name="France"><region name="Occitanie (région administrative)"><name sortKey="Laffont, Sophie" sort="Laffont, Sophie" uniqKey="Laffont S" first="Sophie" last="Laffont">Sophie Laffont</name></region><name sortKey="Blanquart, Eve" sort="Blanquart, Eve" uniqKey="Blanquart E" first="Eve" last="Blanquart">Eve Blanquart</name><name sortKey="Cenac, Claire" sort="Cenac, Claire" uniqKey="Cenac C" first="Claire" last="Cénac">Claire Cénac</name><name sortKey="Girard, Jean Philippe" sort="Girard, Jean Philippe" uniqKey="Girard J" first="Jean-Philippe" last="Girard">Jean-Philippe Girard</name><name sortKey="Guery, Jean Charles" sort="Guery, Jean Charles" uniqKey="Guery J" first="Jean-Charles" last="Guéry">Jean-Charles Guéry</name><name sortKey="Laverny, Gilles" sort="Laverny, Gilles" uniqKey="Laverny G" first="Gilles" last="Laverny">Gilles Laverny</name><name sortKey="Metzger, Daniel" sort="Metzger, Daniel" uniqKey="Metzger D" first="Daniel" last="Metzger">Daniel Metzger</name><name sortKey="Pelletier, Lucette" sort="Pelletier, Lucette" uniqKey="Pelletier L" first="Lucette" last="Pelletier">Lucette Pelletier</name><name sortKey="Savignac, Magali" sort="Savignac, Magali" uniqKey="Savignac M" first="Magali" last="Savignac">Magali Savignac</name><name sortKey="Seillet, Cyril" sort="Seillet, Cyril" uniqKey="Seillet C" first="Cyril" last="Seillet">Cyril Seillet</name></country><country name="Australie"><region name="Victoria (État)"><name sortKey="Belz, Gabrielle T" sort="Belz, Gabrielle T" uniqKey="Belz G" first="Gabrielle T" last="Belz">Gabrielle T. 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