Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation

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

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.

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Asthma / drug therapy
  • Asthma / immunology
  • Cell Proliferation / drug effects
  • Female
  • Flow Cytometry
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Interleukin-13 / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-33 / metabolism
  • Lymphocytes / drug effects*
  • Lymphocytes / immunology
  • Lymphocytes / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Phosphorylation / drug effects
  • STAT5 Transcription Factor / metabolism
  • Testosterone / therapeutic use*
  • Young Adult

Substances

  • Interleukin-13
  • Interleukin-2
  • Interleukin-33
  • STAT5 Transcription Factor
  • Testosterone