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REVIEW article

Front. Pharmacol.

Sec. Ethnopharmacology

This article is part of the Research TopicImmunomodulatory Natural Products - Their Pharmacological and Therapeutic PotentialView all 20 articles

Pharmacological Mechanisms of Traditional Chinese Medicine Metabolites in Regulating Treg Cells: An Integrative Pathway Review

Provisionally accepted
Wang  ChaoWang Chao1Lin  HengLin Heng1Ye  ZhenzhongYe Zhenzhong1Yuan  QingYuan Qing2*Wenzhe  MaWenzhe Ma1*
  • 1Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, Macau Region, China
  • 2Department of Immunology, School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, China

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

Background: Regulatory T cells (Tregs), characterized by the transcription factor Foxp3, play a pivotal role in maintaining immune homeostasis, preventing autoimmunity, and contributing to tumor immune evasion. Traditional Chinese Medicine (TCM), with its long history of clinical application, exerts unique regulatory effects on immune responses. However, a comprehensive mechanistic synthesis of TCM-mediated Treg regulation remains lacking. Methods: We reviewed studies from PubMed up to August 2025, focusing on molecular, cellular, and microbiota-related mechanisms by which TCM modulates Tregs. Identified evidence was synthesized into four major mechanisms and further integrated into three regulatory axes. Results: TCM regulates Tregs through four mechanisms: (1) Foxp3 expression regulation mechanisms; (2) IL-2 receptor pathway mechanisms; (3) Regulation of other Treg surface molecules; and (4) Gut microbiota modulation mechanisms. These four mechanisms converge into three regulatory axes: the core execution axis (direct Foxp3 control), the upstream regulatory axis (cytokine and receptor crosstalk), and the cross-boundary integration axis (gut microbiota–immune interactions). Conclusion: This review proposes an integrated framework that refines four regulatory mechanisms into three axes, highlighting the multi-layered and interconnected pathways through which TCM shapes Treg biology. This systems-level perspective provides a theoretical basis for developing TCM-derived strategies in immune-mediated diseases and cancer immunotherapy. Keywords: Traditional Chinese medicine, Regulatory T cells, Foxp3, Immunomodulation, Mechanisms

Keywords: Traditional Chinese Medicine, regulatory T cells, Foxp3, Immunomodulation, mechanisms

Received: 13 Nov 2024; Accepted: 21 Nov 2025.

Copyright: © 2025 Chao, Heng, Zhenzhong, Qing and Ma. 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:
Yuan Qing, qingyuan@swmu.edu.cn
Wenzhe Ma, wzma@must.edu.mo

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