MINI REVIEW article
Front. Immunol.
Sec. T Cell Biology
This article is part of the Research TopicThe transcriptional and metabolic role of Foxp3 in regulatory T cellsView all 4 articles
Metabolic Regulation of Regulatory T Cells: Mechanisms, Heterogeneity, and Implications in Disease
Provisionally accepted
- 1Harvard Medical School, Boston, United States
- 2Division of Immunology, Boston Children’s Hospital, Boston, Massachusetts, US, Boston, United States
- 3Department of Otolaryngology Head and Neck Surgery, Shanghai Key Laboratory of Sleep Disordered Breathing, Otolaryngological Institute of Shanghai Jiao Tong University, China, Shanghai, China
- 4Institute of Regenerative Medicine and Biotherapy, INSERM, University of Montpellier, Montpellier, France., Montpellier, France
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Regulatory T (Treg) cells are essential for maintaining immune tolerance, preventing autoimmune responses, and supporting tissue repair. Tregs employ a flexible and diverse metabolic program that includes glycolysis, oxidative phosphorylation (OXPHOS), fatty acid oxidation, and lipid metabolism compared to conventional T cells, which largely rely on glycolysis to fuel their proliferation and function. This flexibility allows Tregs to adapt in different tissue environments while sustaining their suppressive activity. Thymic-derived (tTregs), peripheral (pTregs), and induced (iTregs) exhibit distinct metabolic profiles that influence their stability, proliferation, and suppressive capacity. These metabolic pathways are controlled by key regulators such as mTOR, LKB1, and Foxp3, while environmental cues, including nutrient availability, hypoxia, and microbiota-derived metabolites, further shape Treg function. Dysregulation of these pathways can compromise tolerance and contribute to immune-mediated diseases, chronic infections, cancer, and metabolic disorders. In this mini review, we summarize recent insights into the heterogeneity of Treg metabolism, highlighting how metabolic reprogramming underpins their immunoregulatory roles. We also explore therapeutic opportunities for targeting Treg metabolism and discuss future directions leveraging single-cell and spatial technologies to map context-specific metabolic programs in vivo.
Keywords: regulatory T cells, Foxp3, Metabolism, Immune Tolerance, Diseases
Received: 21 Oct 2025; Accepted: 28 Nov 2025.
Copyright: © 2025 Getachew, Hu and Benamar. 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: Mehdi Benamar
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