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ORIGINAL RESEARCH article

Front. Immunol.

Sec. T Cell Biology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1656632

This article is part of the Research TopicFrom a Drop to Discovery: The Potential of Peripheral Blood for Biomedical ResearchView all 4 articles

Altered Th17/Treg Balance and Therapeutic Targeting of RORγ in Primary Focal Hyperhidrosis

Provisionally accepted
Min  LinMin LinJianbo  LinJianbo LinQuan  DuQuan DuYuanrong  TuYuanrong TuJianfeng  ChenJianfeng Chen*
  • First Affiliated Hospital of Fujian Medical University, Fuzhou, China

The final, formatted version of the article will be published soon.

Primary focal hyperhidrosis (PFH) significantly impacts patients' physical and mental health, yet its underlying mechanisms remain unclear. 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 RORγ inverse agonist. 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-β1 levels were observed in PFH serum. Sweat glands showed increased RORγt and decreased FOXP3 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. PFH is associated with a Th17/Treg immune imbalance. SR2211 alleviated hyperhidrosis and Th17-related inflammation in mice, highlighting the potential of targeting the RORγ–Th17 axis as a therapeutic strategy for PFH.

Keywords: Immune imbalance, Primary focal hyperhidrosis (PFH), Th17 cell, Treg cell, RORγ

Received: 16 Jul 2025; Accepted: 03 Oct 2025.

Copyright: © 2025 Lin, Lin, Du, Tu and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Jianfeng Chen, chenjianfeng@fjmu.edu.cn

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