Breakthroughs in basic mechanism research and clinical translation prospects of regulatory T cells

doi:10.3969/j.issn.1674-8115.2026.04.001

Abstract

Abstract:

Immune tolerance serves as the core cornerstone for maintaining the homeostasis of the body's immune system. Once this sophisticated regulatory mechanism is disrupted, it will directly induce a series of major diseases, including autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus, as well as tumor immune escape and organ transplant rejection, seriously endangering human life and health. The 2025 Nobel Prize in Physiology or Medicine was awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi in recognition of their pioneering contributions to the field of peripheral immune tolerance—successfully identifying CD4⁺CD25⁺FOXP3⁺ regulatory T cells (T_reg) and their core regulatory gene, forkhead box P3 (FOXP3), and establishing the core theoretical framework of the “FOXP3-T_reg-immune tolerance” axis, which has laid a solid foundation for subsequent research in this field. This review systematically combs the historical context of T_reg and FOXP3 research, clearly presenting the evolutionary trajectory of the field from the early exploration of immune tolerance phenomena to the identification of key cell subsets and regulatory genes. It focuses on key advances in recent years, comprehensively covering core contents such as the refined classification and developmental characteristics of T_reg subtypes, the multi-dimensional expansion of the FOXP3 regulatory network, the functional mechanisms of T_reg in various diseases, and breakthrough achievements in clinical translation. Finally, focusing on the bottlenecks in the clinical translation of T_reg therapies, this review provides perspectives on future development directions.

Key words: regulatory T cell (T_reg), forkhead box P3 (FOXP3), immune tolerance, immune homeostasis, clinical translation

CLC Number:

R392.12

Wang Zhen, Zhang Nan, Shen Yibing, Li Dan, Peng Cheng, Gu Zhidong, Li Bin. Breakthroughs in basic mechanism research and clinical translation prospects of regulatory T cells[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(4): 415-426.

Figures/Tables 2

TrendMD

References 78

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