Testosterone Decreases House Dust Mite-Induced Type 2 and IL-17A-Mediated Airway Inflammation.
J Immunol
; 201(7): 1843-1854, 2018 10 01.
Article
em En
| MEDLINE
| ID: mdl-30127088
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Hipersensibilidade Respiratória
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Asma
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Testosterona
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Fatores Sexuais
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Células Th2
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Eosinófilos
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Células Th17
Tipo de estudo:
Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article