Format

Send to

Choose Destination
J Immunol. 2018 Oct 1;201(7):1843-1854. doi: 10.4049/jimmunol.1800293. Epub 2018 Aug 20.

Testosterone Decreases House Dust Mite-Induced Type 2 and IL-17A-Mediated Airway Inflammation.

Author information

1
Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232; and.
2
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232.
3
Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232; and dawn.newcomb@vanderbilt.edu.

Abstract

As adults, women are twice as likely as men to have asthma; however, the mechanisms explaining this sexual dimorphism remain unclear. Increased type 2 cytokines and/or IL-17A, leading to increased airway eosinophils and neutrophils, respectively, are associated with asthma. Previous studies showed that testosterone, signaling through the androgen receptor (AR), decreased Th2-mediated allergic inflammation and type 2 innate immune responses during allergic inflammation. Therefore, we hypothesized that testosterone and AR signaling attenuate type 2 and IL-17A-mediated airway inflammation. To test our hypothesis, sham-operated and gonadectomized female and male mice were intranasally challenged with house dust mite (HDM) or vehicle (PBS) for 3 wk. Testosterone decreased and ovarian hormones increased HDM-induced eosinophilic and neutrophilic inflammation, IgE production, and airway hyperresponsiveness, as well as decreased the numbers of IL-13+ CD4 Th2 cells and IL-17A+ CD4 Th17 cells in the lung. Next, using wild-type male and female mice and ARtfm male mice that are unable to signal through the AR, we determined AR signaling intrinsically attenuated IL-17A+ Th17 cells but indirectly decreased IL-13+ CD4 Th2 cells in the lung by suppressing HDM-induced IL-4 production. In vitro Th2 and Th17 differentiation experiments showed AR signaling had no direct effect on Th2 cell differentiation but decreased IL-17A protein expression and IL-23R mRNA relative expression from Th17 cells. Combined, these findings show AR signaling attenuated type 2 and IL-17A inflammation through different mechanisms and provide a potential explanation for the increased prevalence of asthma in women compared with men.

PMID:
30127088
PMCID:
PMC6143420
[Available on 2019-10-01]
DOI:
10.4049/jimmunol.1800293

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center