Targeting androgen signaling in ILC2s protects from IL-33–driven lung inflammation, independently of KLRG1

Autor: Blanquart, Eve, Mandonnet, Audrey, Mars, Marion, Cenac, Claire, Anesi, Nina, Mercier, Pascale, Audouard, Christophe, Roga, Stephane, Serrano de Almeida, Gilberto, Bevan, Charlotte, Girard, Jean-Philippe, Pelletier, Lucette, Laffont, Sophie, Guéry, Jean-Charles
Přispěvatelé: Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie et de biologie structurale (IPBS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre de biologie du développement (CBD), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Imperial College London, laffont-pradines, sophie, Toulouse Institute for Infectious and Inflammatory Diseases, University of Toulouse, CNRS, INSERM, UPS, Toulouse, France. (Infinity), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Male
KLRG1
MESH: Signal Transduction
[SDV.IMM] Life Sciences [q-bio]/Immunology
MESH: Lung / pathology
androgen signaling
MESH: Mice
Knockout
[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity
ILC2
MESH: Testosterone / pharmacology
MESH: Pneumonia / immunology
MESH: Mice
Inbred C57BL
Animals
Lectins
C-Type
Testosterone
Sex differences in asthma
MESH: Animals
Lymphocytes
MESH: Pneumonia / pathology
Receptors
Immunologic
[SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology
Lung
[SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity
ComputingMilieux_MISCELLANEOUS
Mice
Knockout
Sex Characteristics
lung inflammation
MESH: Androgens / pharmacology
Pneumonia
MESH: Lung / immunology
Interleukin-33
MESH: Receptors
Immunologic / immunology
MESH: Male
Mice
Inbred C57BL
MESH: Lymphocytes / immunology
MESH: Lectins
C-Type / immunology
MESH: Interleukin-33 / immunology
Androgens
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
MESH: Female
[SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology
Signal Transduction
MESH: Sex Characteristics
Zdroj: Journal of Allergy and Clinical Immunology
Journal of Allergy and Clinical Immunology, 2022, 149 (1), pp.237-251.e12. ⟨10.1016/j.jaci.2021.04.029⟩
Journal of Allergy and Clinical Immunology, Elsevier, 2021, ⟨10.1016/j.jaci.2021.04.029⟩
ISSN: 0091-6749
Popis: International audience; Background: Allergic asthma is more severe and frequent in women than in men. In male mice, androgens negatively control group 2 innate lymphoid cell (ILC2) development and function by yet unknown mechanisms.Objectives: We sought to investigate the impact of androgen on ILC2 homeostasis and IL-33-mediated inflammation in female lungs. We evaluated the role of androgen receptor (AR) signaling and the contribution of the putative inhibitory receptor killer cell lectin-like receptor G1 (KLRG1).Methods: Subcutaneous pellets mimicking physiological levels of androgen were used to treat female mice together with mice expressing a reporter enzyme under the control of androgen response elements and mixed bone marrow chimeras to assess the cell-intrinsic role of AR activation within ILC2s. We generated KLRG1-deficient mice.Results: We established that lung ILC2s express a functionally active AR that can be in vivo targeted with exogenous androgens to negatively control ILC2 homeostasis, proliferation, and function. Androgen signaling upregulated KLRG1 on ILC2s, which inhibited their proliferation on E-cadherin interaction. Despite evidence that KLRG1 impaired the competitive fitness of lung ILC2s during inflammation, KLRG1 deficiency neither alters in vivo ILC2 numbers and functions, nor did it lead to hyperactive ILC2s in either sexes.Conclusions: AR agonists can be used in vivo to inhibit ILC2 homeostatic numbers and ILC2-dependent lung inflammation through cell-intrinsic AR activation. Although androgen signals in ILC2s to upregulate KLRG1, we demonstrate that KLRG1 is dispensable for androgen-mediated inhibition of pulmonary ILC2s.
Databáze: OpenAIRE
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