2025年诺贝尔生理学或医学奖——外周免疫耐受机制的里程碑发现及其临床意义

doi:10.3969/j.issn.1006-7795.2025.06.025

首都医科大学学报 ›› 2025, Vol. 46 ›› Issue (6): 1152-1156.doi: 10.3969/j.issn.1006-7795.2025.06.025

2025年诺贝尔生理学或医学奖——外周免疫耐受机制的里程碑发现及其临床意义

于明航^1,2,3,4，王建新^1,2,3，夏妙然⁵，陈萍⁵，王玺^1,2,3,4*

1.传染病溯源预警与智能决策全国重点实验室,首都医科大学附属北京地坛医院,北京 100015; 2.首都医科大学附属北京地坛医院传染病研究所, 病毒性传染病研究北京市重点实验室,首都医科大学附属北京地坛医院国家传染病医学中心,北京 100015; 3.北京市感染性疾病研究中心,北京 100015; 4.首都医科大学肿瘤学系,北京 100069；5.首都医科大学基础医学院免疫学系, 北京 100069

收稿日期:2025-10-20 修回日期:2025-10-24 出版日期:2025-12-21 发布日期:2025-12-19
通讯作者: 王玺 E-mail:xiwang@ccmu.edu.cn

The 2025 Nobel Prize in Physiology or Medicine: discoveries in peripheral immune tolerance mechanisms and their clinical significance

Yu Minghang^1,2,3,4, Wang Jianxin^1,2,3, Xia Miaoran⁵, Chen Ping⁵, Wang Xi^1,2,3,4*

1.National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China；2.Beijing Key Laboratory of Viral Infectious Diseases, Institute of Infectious Diseases, National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China； 3.Beijing Institute of Infectious Diseases, Beijing 100015, China; 4.Department of Oncology, Capital Medical University, Beijing 100069, China; 5.Department of Immunology, School of Basic Medical Science, Capital Medical University, Beijing 100069, China

Received:2025-10-20 Revised:2025-10-24 Online:2025-12-21 Published:2025-12-19

摘要/Abstract

摘要： 北京时间2025年10月6日，诺贝尔生理学或医学奖再度落于免疫学领域，瑞典卡罗琳斯卡学院诺贝尔大会决定将 2025 年诺贝尔生理学或医学奖授予美国科学家玛丽·E·布伦科（Mary E.Brunkow）、弗雷德·拉姆斯德尔（Fred Ramsdell）和日本科学家坂口志文（Shimon Sakaguchi），以表彰他们在外周免疫耐受机制方面的开创性发现。本文将介绍三位科学家的简历、主要科学贡献和他们科学发现的意义。

关键词: 诺贝尔生理学或医学奖, 中枢免疫耐受, 外周免疫耐受, 调节性T细胞, 叉头框P3基因, 免疫治疗

Abstract: On October 6, 2025, the Nobel Prize in Physiology or Medicine has once again been conferred upon the field of immunology. The Nobel Assembly at the Karolinska Institute has awarded the 2025 Nobel Prize in Physiology or Medicine to American scientists Mary E.Brunkow and Fred Ramsdell, and Japanese scientist Shimon Sakaguchi in recognition of their pioneering discoveries concerning mechanisms of peripheral immune tolerance. This article presents the biographies of the three scientists, summarizes their major scientific contributions, and highlights the significance of their findings.

Key words: Nobel Prize in Physiology or Medicine, central immune tolerance, peripheral immune tolerance, Treg, Foxp3, immunotherapy

中图分类号:

R392.1

于明航, 王建新, 夏妙然, 陈萍, 王玺. 2025年诺贝尔生理学或医学奖——外周免疫耐受机制的里程碑发现及其临床意义[J]. 首都医科大学学报, 2025, 46(6): 1152-1156.

Yu Minghang, Wang Jianxin, Xia Miaoran, Chen Ping, Wang Xi. The 2025 Nobel Prize in Physiology or Medicine: discoveries in peripheral immune tolerance mechanisms and their clinical significance[J]. Journal of Capital Medical University, 2025, 46(6): 1152-1156.

参考文献

［1］Anon. Nobel Prize in Physiology or Medicine 2025［EB/OL］//(2025-10-06)［2025-10-08］. https://www.nobelprize.org/prizes/medicine/2025/summary/.
［2］Bluestone J A, Anderson M. Tolerance in the age of immunotherapy［J］. N Engl J Med, 2020, 383(12): 1156－1166.
［3］Nishizuka Y, Sakakura T. Thymus and reproduction: sex-linked dysgenesia of the gonad after neonatal thymectomy in mice［J］. Science, 1969, 166(3906): 753－755.
［4］Sakaguchi S, Fukuma K, Kuribayashi K, et al. Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease［J］. J Exp Med, 1985, 161(1): 72－87.
［5］Sakaguchi S, Sakaguchi N, Asano M, et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases［J］. J Immunol, 1995, 155(3): 1151－1164.
［6］Sakaguchi S. Regulatory T cells: key controllers of immunologic self-tolerance［J］. Cell, 2000, 101(5): 455－458.
［7］Clark L B, Appleby M W, Brunkow M E, et al. Cellular and molecular characterization of the scurfy mouse mutant［J］. J Immunol, 1999, 162(5): 2546－2554.
［8］Brunkow M E, Jeffery E W, Hjerrild K A, et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse［J］. Nat Genet, 2001, 27(1): 68－73.
［9］Wildin R S, Ramsdell F, Peake J, et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy［J］. Nat Genet, 2001, 27(1): 18－20.
［10］Schubert L A, Jeffery E, Zhang Y, et al. Scurfin (FOXP3) acts as a repressor of transcription and regulates T cell activation［J］. J Biol Chem, 2001, 276(40): 37672－37679.
［11］Bennett C L, Christie J, Ramsdell F, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3［J］. Nat Genet, 2001, 27(1): 20－21.
［12］Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3［J］. Science, 2003, 299(5609): 1057－1061.
［13］Tay C, Tanaka A, Sakaguchi S. Tumor-infiltrating regulatory T cells as targets of cancer immunotherapy［J］. Cancer Cell, 2023, 41(3): 450－465.
［14］Liu X N, Zhang W Q, Han Y C, et al. FOXP3+regulatory T cell perturbation mediated by the IFNγ-STAT1-IFITM3 feedback loop is essential for anti-tumor immunity［J］. Nat Commun, 2024, 15(1): 122.
［15］Niu C Y, Wei H, Pan X X, et al. Foxp3 confers long-term efficacy of chimeric antigen receptor-T cells via metabolic reprogramming［J］. Cell Metab, 2025, 37(6): 1426－1441, e7.
［16］Ding R, Yu X Y, Hu Z L, et al. Lactate modulates RNA splicing to promote CTLA-4 expression in tumor-infiltrating regulatory T cells［J］. Immunity, 2024, 57(3): 528－540, e6.
［17］Ghobadinezhad F, Ebrahimi N, Mozaffari F, et al. The emerging role of regulatory cell-based therapy in autoimmune disease［J］. Front Immunol, 2022, 13: 1075813.
［18］Zhang R Z, Zhao Y Y, Chen X M, et al. Low-dose IL-2 therapy in autoimmune diseases: an update review［J］. Int Rev Immunol, 2024, 43(3): 113－137.
［19］He J, Zhang X, Wei Y B, et al. Low-dose interleukin-2 treatment selectively modulates CD4(+) T cell subsets in patients with systemic lupus erythematosus［J］. Nat Med, 2016, 22(9): 991－993.

[1]	汪婧雯, 李振军, 吕亮成, 姚晓雨, 丁宁. B细胞受体信号通路在B细胞淋巴瘤中的作用及靶向治疗策略[J]. 首都医科大学学报, 2025, 46(3): 436-441.
[2]	张文秀, 熊阳, 于明航, 王玺. STAT3在肿瘤免疫应答中的作用机制研究进展[J]. 首都医科大学学报, 2025, 46(3): 442-447.
[3]	谭乃川, 孟艳, 赵恒. 微小 RNA，巨大的影响——Victor Ambros 和 Gary Ruvkun 荣获 2024 年诺贝尔生理学或医学奖[J]. 首都医科大学学报, 2024, 45(6): 1122-1130.
[4]	李铁铮, 胥凯凯, 邓钰卿, 王沛豪, 秦齐, 郭康顺, 王炳仁, 常栋, 崔永. PD-1单抗联合化学药物治疗在局部晚期非小细胞肺癌新辅助治疗中的疗效和安全性分析[J]. 首都医科大学学报, 2024, 45(4): 636-641.
[5]	王居巳, 宋伟安, 狄守印, 刘军强, 范博士, 周少华, 岳彩迎, 赵嘉华, 陈思禹, 龚太乾. 新辅助化疗联合免疫抑制剂对Ⅲ期非小细胞肺癌治疗有效性分析[J]. 首都医科大学学报, 2024, 45(4): 660-665.
[6]	郝卓鸿, 云铎, 张颖, 李卉惠, 林海珊, 崔永, 赵磊. 非小细胞肺癌围手术期免疫治疗研究进展———新辅助免疫治疗进展[J]. 首都医科大学学报, 2024, 45(4): 666-677.
[7]	周妍, 吴巍. Katalin Karikó 和Drew Weissman助力研发抗新型冠状病毒mRNA 疫苗荣获2023年诺贝尔生理学或医学奖[J]. 首都医科大学学报, 2023, 44(5): 889-894.

2025年诺贝尔生理学或医学奖——外周免疫耐受机制的里程碑发现及其临床意义

The 2025 Nobel Prize in Physiology or Medicine: discoveries in peripheral immune tolerance mechanisms and their clinical significance

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 7

编辑推荐

Metrics

本文评价