Fiche publication
Date publication
mai 2017
Journal
The Journal of experimental medicine
Auteurs
Membres identifiés du Cancéropôle Est :
Dr METZGER Daniel
,
Dr LAVERNY Gilles
Tous les auteurs :
Laffont S, Blanquart E, Savignac M, Cénac C, Laverny G, Metzger D, Girard JP, Belz GT, Pelletier L, Seillet C, Guéry JC
Lien Pubmed
Résumé
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.
Mots clés
Androgens, metabolism, Animals, Asthma, complications, Castration, Cell Proliferation, drug effects, Disease Susceptibility, Female, Hypersensitivity, complications, Immunity, Innate, immunology, Interleukin-33, metabolism, Lung, immunology, Lymphocyte Count, Lymphocytes, immunology, Male, Mice, Inbred C57BL, Pneumonia, complications, Pyroglyphidae, immunology, Receptors, Androgen, metabolism, Sexism, Signal Transduction
Référence
J. Exp. Med.. 2017 May;:
