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J Exp Med. 2017 Jun 5;214(6):1581-1592. doi: 10.1084/jem.20161807. Epub 2017 May 8.

Androgen signaling negatively controls group 2 innate lymphoid cells.

Author information

1
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.
2
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.
3
Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, 31077 Toulouse, France.
4
The Walter and Elisa Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria 3052, Australia.
5
Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
6
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.
7
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.

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.

PMID:
28484078
PMCID:
PMC5461006
DOI:
10.1084/jem.20161807
[Indexed for MEDLINE]
Free PMC Article

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