《生命科学》 2026, 38(4): 615-624

直面Treg疗法在1型糖尿病中的挑战：最新研究启示

陈 晔^1,2,3 , 刘 玲^1,2,3 , 郑颂国^1,2,3,*

¹上海交通大学医学院细胞和基因治疗研究院，上海 201600 ²上海交通大学创新免疫治疗全国重点实验室，上海 201600 ³上海交通大学医学院附属松江医院，上海 201600

摘　要：

1型糖尿病（type 1 diabetes，T1D）是一种由自身免疫性异常反应破坏胰岛β细胞引发的疾病。调节性T细胞（regulatory T cells，Treg）为一类具有免疫抑制和调控作用的免疫细胞亚群，合理使用这些细胞有望成为自身免疫性疾病的潜在防治策略。目前Treg疗法包括天然存在的Treg（natural regulatory T cells，nTreg）、TGF-β诱导的Treg（induced regulatory T cells，iTreg）、通用型Treg、抗原特异性Treg及基因工程化Treg，每种方法均具有独特的优势与局限性。研究表明，工程化T细胞受体（T cell receptor，TCR）和嵌合抗原受体（chimeric antigen receptor，CAR）技术能够介导抗原特异性抑制，为T1D治疗提供了新的思路，但其临床应用仍面临疾病特异性抗原鉴定、Treg稳定性提升、归巢能力增强及细胞衰竭等关键问题。未来的研究需要聚焦于抗原鉴定、功能优化及体内监测，同时个体化纠正Treg缺陷通路，以推动工程化Treg的临床转化。本文综述了Treg疗法在T1D治疗中的最新研究进展，探讨了其面临的挑战及潜在的优化策略。

通讯作者：郑颂国 , Email:Song.Zheng@shsmu.edu.cn

Overcoming the challenges of Treg therapy in type 1 diabetes: Insights from recent research

CHEN Ye^1,2,3 , LIU Ling^1,2,3 , ZHENG Song-Guo^1,2,3,*

¹School of Cell and Gene Therapy, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China ²State Key Lab of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 201600, China ³Shanghai Songjiang Hospital Affiliated to the Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China

Abstract:

Type 1 diabetes (T1D) is an autoimmune disorder characterized by T cell-mediated destruction of pancreatic β cells. Regulatory T cells (Treg) play a pivotal role in maintaining immune homeostasis and suppressing autoimmunity, making them a promising therapeutic strategy for T1D. Current Treg-based therapies include natural Treg (nTreg), TGF-β-induced Treg (iTreg), universal Treg, antigen-specific Treg, and engineered Treg expressing T cell receptors (TCRs) or chimeric antigen receptors (CARs). While nTreg and iTreg have shown efficacy in preclinical models, their clinical application is limited by instability under inflammatory conditions, low numbers, and non-specific immunosuppression. Engineered TCR and CAR-Treg enable antigen-specific suppression, enhancing targeting, homing to pancreatic islets, and immune-modulatory potency, yet face challenges such as disease-specific antigen identification, Treg stability, exhaustion, and off-target effects. Clinical trials indicate that adoptive Treg therapy is generally safe but often transient in effect, emphasizing the need for early intervention, repeated dosing, or combinatorial strategies (e.g., low-dose IL-2, B cell depletion). Emerging approaches, including integration of chemokine receptor modulation, signal-inducible complexes, and ex vivo engineering to enhance persistence, homing, and suppressive function, hold promise for improving therapeutic outcomes. Future research should focus on optimizing antigen specificity, functional stability, in vivo persistence, and personalized correction of Treg deficiencies to achieve durable immune tolerance. Collectively, advances in TCR and CAR Treg engineering are ushering a new era in Treg-based immunotherapy for T1D, offering potential for safe and effective disease-modifying interventions.

Communication Author：ZHENG Song-Guo , Email:Song.Zheng@shsmu.edu.cn