{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T00:10:54Z","timestamp":1760746254180,"version":"build-2065373602"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Primary focal hyperhidrosis (PFH) significantly impacts patients\u2019 physical and mental health, yet its underlying mechanisms remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study involved 80 healthy controls and 60 patients each with primary palmar (PPH), craniofacial (PCH), or axillary hyperhidrosis (PAH). Peripheral blood mononuclear cells (PBMCs) were analyzed via flow cytometry to assess Th17 and Treg cell populations. Cytokine levels were measured in patient serum using ELISA, while sweat gland tissue from PAH patients underwent gene expression analysis. A pilocarpine-induced mouse model of hyperhidrosis was used to test SR2211, a ROR\u03b3 inverse agonist.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PFH patients exhibited a disrupted Th17\/Treg balance, with increased Th17 and decreased Treg cells across all subtypes compared to controls. Elevated IL-17 and IL-6 and reduced IL-10 and TGF-\u03b21 levels were observed in PFH serum. Sweat glands showed increased <jats:italic>ROR\u03b3t<\/jats:italic> and decreased <jats:italic>FOXP3<\/jats:italic> expression. In mice, SR2211 treatment reduced sweat secretion, secretory granules, and serum acetylcholine. It also lowered Th17 infiltration, serum IL-17\/IL-6, and IL-17A expression in sweat glands.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>PFH is associated with a Th17\/Treg immune imbalance. SR2211 alleviated hyperhidrosis and Th17-related inflammation in mice, highlighting the potential of targeting the ROR\u03b3\u2013Th17 axis as a therapeutic strategy for PFH.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1656632","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T05:31:21Z","timestamp":1760679081000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Altered Th17\/Treg balance and therapeutic targeting of ROR\u03b3 in primary focal 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