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Gandhi VD, Cephus JY, Norlander AE, et al. Androgen receptor signaling promotes Treg suppressive function during allergic airway inflammation. J Clin Invest. 2022;doi: 10.1172/JCI153397.
Gandhi, V. D., Cephus, J. Y., Norlander, A. E., Chowdhury, N. U., Zhang, J., Ceneviva, Z. J., Tannous, E., Polosukhin, V. V., Putz, N. D., Wickersham, N., Singh, A., Ware, L. B., Bastarache, J. A., Shaver, C. M., Chu, H. W., Peebles, R. S., & Newcomb, D. C. (2022). Androgen receptor signaling promotes Treg suppressive function during allergic airway inflammation. The Journal of clinical investigation, . https://doi.org/10.1172/JCI153397
Gandhi, Vivek D, et al. "Androgen receptor signaling promotes Treg suppressive function during allergic airway inflammation." The Journal of clinical investigation vol. (2022). doi: https://doi.org/10.1172/JCI153397
Gandhi VD, Cephus JY, Norlander AE, Chowdhury NU, Zhang J, Ceneviva ZJ, Tannous E, Polosukhin VV, Putz ND, Wickersham N, Singh A, Ware LB, Bastarache JA, Shaver CM, Chu HW, Peebles RS, Newcomb DC. Androgen receptor signaling promotes Treg suppressive function during allergic airway inflammation. J Clin Invest. 2022 Jan 13; doi: 10.1172/JCI153397. Epub 2022 Jan 13. PMID: 35025767.
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J Clin Invest. 2022 Jan 13; doi: 10.1172/JCI153397. Epub 2022 Jan 13.

Androgen receptor signaling promotes Treg suppressive function during allergic airway inflammation.

The Journal of clinical investigation

Vivek D Gandhi, Jacqueline-Yvonne Cephus, Allison E Norlander, Nowrin U Chowdhury, Jian Zhang, Zachary J Ceneviva, Elie Tannous, Vasiliy V Polosukhin, Nathan D Putz, Nancy Wickersham, Amrit Singh, Lorraine B Ware, Julie A Bastarache, Ciara M Shaver, Hong Wei Chu, Ray S Peebles, Dawn C Newcomb

Affiliations

  1. Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America.
  2. Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, United States of America.
  3. Prevention of Organ Failure (PROOF) Centre of Excellence, University of British Columbia, Vacouver, Canada.
  4. Department of Medicine, National Jewish Health, Denver, United States of America.

PMID: 35025767 DOI: 10.1172/JCI153397

Abstract

Women have higher prevalence of asthma compared to men. In asthma, allergic airway inflammation is initiated by IL-33 signaling through ST2, leading to increased IL-4, IL-5, and IL-13 production and eosinophil infiltration. Foxp3+ Tregs suppress and ST2+ Tregs promote allergic airway inflammation. Clinical studies showed the androgen, dehydroepiandrosterone (DHEA), reduced asthma symptoms in patients, and mouse studies showed androgen receptor (AR) signaling decreased allergic airway inflammation. Yet, the role of AR signaling on lung Tregs remains unclear. Using AR deficient and Foxp3 fate-mapping mice, we determined that AR signaling increased Treg suppression during Alternaria extract (Alt Ext, allergen) challenge by stabilizing Foxp3+ Tregs and limiting the number of ST2+ ex-Tregs and IL-13+ Th2 and ex-Tregs. AR signaling also decreased Alt Ext-induced ST2+ Tregs in mice by limiting Gata2 expression, a transcription factor for ST2, and by decreasing Alt Ext-induced IL-33 production from murine airway epithelial cells. We confirmed our findings in human cells where 5α-dihydrotestosterone (DHT), an androgen, decreased IL-33-induced ST2 expression in lung Tregs and decreased Alt Ext induced IL-33 secretion in human bronchial epithelial cells. Our findings showed that AR signaling stabilized Treg suppressive function, providing a mechanism for the sex difference in asthma.

Keywords: Asthma; Inflammation; Pulmonology; Sex hormones; T cells

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