REVIEW article
Front. Endocrinol.
Sec. Diabetes: Molecular Mechanisms
This article is part of the Research TopicTregs as medicine: Translational advances and clinical frontiersView all articles
Regulatory T cell Dysfunction and Immunotherapeutic Breakthroughs in Type 1 Diabetes
Provisionally accepted
- 1Huazhong University of Science and Technology, Wuhan, China
- 2Hamad Bin Khalifa University Qatar Biomedical Research Institute, Doha, Qatar
- 3Shanxi Bethune Hospital, Taiyuan, China
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Type 1 diabetes (T1D) is characterized by the autoimmune destruction of insulin-producing β-cells in the pancreas. Regulatory T cells (Tregs) are essential for maintaining immune tolerance, but they manifest impaired functionality, particularly within the pancreatic microenvironment, during T1D development. This review aimed to discuss Treg biology including the developmental trajectory, phenotypic heterogeneity, and suppressive function, by which we sought to emphasize their compromised role in T1D pathogenesis associated with genetic/epigenetic factors along with impaired cytokine signaling. The unique chemokine receptor expression signature, migratory capacity, and metabolic adaptation of pancreatic Tregs are highlighted, alongside insights from single-cell studies. The evolution of Treg-based immunotherapies is explored, with emphasis on genetically engineered Tregs (EngTregs), which are designed for the stable ectopic expression of FoxP3 and antigen-specific receptors, such as T cell receptors (TCR) or chimeric antigen receptors (CAR). It also highlights advancements in genome-editing and delivery technologies, along with rationally designed combination strategies incorporated into multifunctional cellular products. Despite encouraging preclinical results, significant challenges persist in clinical translation. Overall, this review synthesizes existing knowledge and outlines future directions in Treg biology and immunotherapy, underscoring the potential of next-generation Treg therapy to achieve durable immune tolerance in T1D.
Keywords: Pancreasresident Treg, Regulatory T cells (Tregs), Treg based immunotherapy, Treg dysfunction, Type 1 diabetes (T1D)
Received: 05 Nov 2025; Accepted: 11 Dec 2025.
Copyright: © 2025 Zhou, Rong, Liu, Sun, Wang, Yu and Wang. 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:
Qi-Lin Yu
Cong-Yi Wang
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