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Cell Rep. 2017 Nov 28;21(9):2487-2499. doi: 10.1016/j.celrep.2017.10.110.

Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation.

Author information

1
Department of Medicine, Vanderbilt University Medical Center, T-1221 Medical Center North, 1161 21(st) Avenue, Nashville, TN 37232, USA.
2
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Medical Center North, 1161 21(st) Avenue, Nashville, TN 37232, USA.
3
Department of Medicine and Pathology, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
4
Department of Medicine, Vanderbilt University Medical Center, T-1221 Medical Center North, 1161 21(st) Avenue, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Medical Center North, 1161 21(st) Avenue, Nashville, TN 37232, USA.
5
Department of Medicine, Vanderbilt University Medical Center, T-1221 Medical Center North, 1161 21(st) Avenue, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Medical Center North, 1161 21(st) Avenue, Nashville, TN 37232, USA. Electronic address: dawn.newcomb@vanderbilt.edu.

Abstract

Sex hormones regulate many autoimmune and inflammatory diseases, including asthma. As adults, asthma prevalence is 2-fold greater in women compared to men. The number of group 2 innate lymphoid cells (ILC2) is increased in patients with asthma, and we investigate how testosterone attenuates ILC2 function. In patients with moderate to severe asthma, we determine that women have an increased number of circulating ILC2 compared to men. ILC2 from adult female mice have increased IL-2-mediated ILC2 proliferation versus ILC2 from adult male mice, as well as pre-pubescent females and males. Further, 5α-dihydrotestosterone, a hormone downstream of testosterone, decreases lung ILC2 numbers and IL-5 and IL-13 expression from ILC2. In vivo, testosterone attenuated Alternaria-extract-induced IL-5+ and IL-13+ ILC2 numbers and lung eosinophils by intrinsically decreasing lung ILC2 numbers, as well as by decreasing expression of IL-33 and thymic stromal lymphopoietin (TSLP), ILC2-stimulating cytokines. Collectively, these findings provide a foundational understanding of sexual dimorphism in ILC2 function.

KEYWORDS:

asthma; innate lymphoid cells; sex hormones; testosterone

PMID:
29186686
PMCID:
PMC5731254
DOI:
10.1016/j.celrep.2017.10.110
[Indexed for MEDLINE]
Free PMC Article

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