Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation
Jacqueline-Yvonne Cephus,
Matthew T. Stier,
Hubaida Fuseini,
Jeffrey A. Yung,
Shinji Toki,
Melissa H. Bloodworth,
Weisong Zhou,
Kasia Goleniewska,
Jian Zhang,
Sarah L. Garon,
Robert G. Hamilton,
Vasiliy V. Poloshukin,
Kelli L. Boyd,
R. Stokes Peebles, Jr.,
Dawn C. Newcomb
Affiliations
Jacqueline-Yvonne Cephus
Department of Medicine, Vanderbilt University Medical Center, T-1221 Medical Center North, 1161 21st Avenue, Nashville, TN 37232, USA
Matthew T. Stier
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Medical Center North, 1161 21st Avenue, Nashville, TN 37232, USA
Hubaida Fuseini
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Medical Center North, 1161 21st Avenue, Nashville, TN 37232, USA
Jeffrey A. Yung
Department of Medicine, Vanderbilt University Medical Center, T-1221 Medical Center North, 1161 21st Avenue, Nashville, TN 37232, USA
Shinji Toki
Department of Medicine, Vanderbilt University Medical Center, T-1221 Medical Center North, 1161 21st Avenue, Nashville, TN 37232, USA
Melissa H. Bloodworth
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Medical Center North, 1161 21st Avenue, Nashville, TN 37232, USA
Weisong Zhou
Department of Medicine, Vanderbilt University Medical Center, T-1221 Medical Center North, 1161 21st Avenue, Nashville, TN 37232, USA
Kasia Goleniewska
Department of Medicine, Vanderbilt University Medical Center, T-1221 Medical Center North, 1161 21st Avenue, Nashville, TN 37232, USA
Jian Zhang
Department of Medicine, Vanderbilt University Medical Center, T-1221 Medical Center North, 1161 21st Avenue, Nashville, TN 37232, USA
Sarah L. Garon
Department of Medicine, Vanderbilt University Medical Center, T-1221 Medical Center North, 1161 21st Avenue, Nashville, TN 37232, USA
Robert G. Hamilton
Department of Medicine and Pathology, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA
Vasiliy V. Poloshukin
Department of Medicine, Vanderbilt University Medical Center, T-1221 Medical Center North, 1161 21st Avenue, Nashville, TN 37232, USA
Kelli L. Boyd
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Medical Center North, 1161 21st Avenue, Nashville, TN 37232, USA
R. Stokes Peebles, Jr.
Department of Medicine, Vanderbilt University Medical Center, T-1221 Medical Center North, 1161 21st Avenue, Nashville, TN 37232, USA
Dawn C. Newcomb
Department of Medicine, Vanderbilt University Medical Center, T-1221 Medical Center North, 1161 21st Avenue, Nashville, TN 37232, USA
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.
