Androgen receptor signaling promotes Treg suppressive function during allergic airway inflammation

dc.contributor.authorGandhi, Vivek D.
dc.contributor.authorCephus, Jacqueline-Yvonne
dc.contributor.authorNorlander, Allison E.
dc.contributor.authorChowdhury, Nowrin U.
dc.contributor.authorZhang, Jian
dc.contributor.authorCeneviva, Zachary J.
dc.contributor.authorTannous, Elie
dc.contributor.authorPolosukhin, Vasiliy V.
dc.contributor.authorPutz, Nathan D.
dc.contributor.authorWickersham, Nancy
dc.contributor.authorSingh, Amrit
dc.contributor.authorWare, Lorraine B.
dc.contributor.authorBastarache, Julie A.
dc.contributor.authorShaver, Ciara M.
dc.contributor.authorChu, Hong Wei
dc.contributor.authorPeebles, R. Stokes, Jr.
dc.contributor.authorNewcomb, Dawn C.
dc.contributor.departmentAnatomy, Cell Biology and Physiology, School of Medicine
dc.date.accessioned2025-01-29T12:23:41Z
dc.date.available2025-01-29T12:23:41Z
dc.date.issued2022
dc.description.abstractWomen have higher prevalence of asthma compared with 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 that the androgen dehydroepiandrosterone (DHEA) reduced asthma symptoms in patients, and mouse studies showed that androgen receptor (AR) signaling decreased allergic airway inflammation. Yet the impact 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 cells and ex-Tregs. AR signaling also decreased Alt Ext–induced ST2+ Tregs in mice by limiting expression of Gata2, 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.
dc.eprint.versionFinal published version
dc.identifier.citationGandhi VD, Cephus JY, Norlander AE, et al. Androgen receptor signaling promotes Treg suppressive function during allergic airway inflammation. J Clin Invest. 2022;132(4):e153397. doi:10.1172/JCI153397
dc.identifier.urihttps://hdl.handle.net/1805/45575
dc.language.isoen_US
dc.publisherAmerican Society for Clinical Investigation
dc.relation.isversionof10.1172/JCI153397
dc.relation.journalJournal of Clinical Investigation
dc.rightsPublisher Policy
dc.sourcePMC
dc.subjectInflammation
dc.subjectPulmonology
dc.subjectAsthma
dc.subjectSex hormones
dc.subjectT cells
dc.titleAndrogen receptor signaling promotes Treg suppressive function during allergic airway inflammation
dc.typeArticle
ul.alternative.fulltexthttps://pmc.ncbi.nlm.nih.gov/articles/PMC8843736/
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