Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation

Abstract

<p id="P1">Sex hormones regulate many autoimmune and inflammatory diseases, including asthma. As adults, asthma prevalence is 2-fold greater in women compared to men. Group 2 innate lymphoid cells (ILC2) are increased in asthma, and we investigated how testosterone attenuated ILC2 function. In patients with moderate to severe asthma, we determined that women had increased circulating ILC2 numbers compared to men. In mice, ILC2 from adult females had increased IL-2-mediated ILC2 proliferation versus ILC2 from adult males and pre-pubescent females and males. Further, 5α-dihydrotestosterone, a hormone downstream of testosterone, decreased 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 and cytokine expression as well as decreasing expression of IL-33 and TSLP, ILC2 stimulating cytokines. Collectively, these findings provide a foundational understanding in the sexual dimorphism in ILC2 function. </p><p id="P2"> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/a2f59de9-21f0-40c1-9af0-e6f677206046/PubMedCentral/image/nihms922191u1.jpg"/> </div> </p><p id="P3">Women have higher asthma prevalence compared than men, and ILC2 are increased in patients with asthma. Cephus et al show women with asthma had higher circulating ILC2 numbers compared to men with asthma. Testosterone negatively regulated ILC2 proliferation and cytokine expression as well as ILC2-mediated allergic airway inflammation. </p>