专家解读诺奖生理学或医学奖：调节性T细胞可助力治疗免疫疾病

Core Viewpoint - The Nobel Prize in Physiology or Medicine for 2025 is awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their significant contributions to the discovery of peripheral immune tolerance through regulatory T cells (Tregs) [1][2]. Group 1: Contributions of Awardees - Shimon Sakaguchi first reported the marker molecule CD25 for regulatory T cells in 1995, establishing the CD4+CD25+ cells as Tregs and demonstrating their critical role in preventing autoimmune diseases [2]. - Mary E. Brunkow linked mutations in the Foxp3 gene to the rare autoimmune disease IPEX in 2001, identifying Foxp3 as the "master switch" for Treg function and advancing the field significantly [2]. - Fred Ramsdell contributed to the understanding of the molecular mechanisms of Tregs, revealing the relationship between Foxp3 mutations and IPEX syndrome, thus confirming the importance of Tregs in maintaining immune tolerance [2]. Group 2: Importance of Regulatory T Cells - Regulatory T cells are present in very low numbers but are crucial for maintaining health; even slight changes in their numbers can disrupt immune balance, leading to various diseases [3]. - A decrease in Treg numbers can result in autoimmune or allergic diseases, while an increase can lead to tumors and infections, indicating the potential for targeted therapies to treat immune-related diseases [3][4]. - Compared to most drug treatments, Tregs offer specificity and can minimize side effects associated with treatment toxicity, which may be a significant reason for the Nobel recognition [4]. Group 3: Clinical Application and Challenges - Despite the advantages of Tregs in therapeutic interventions, there are limitations in their clinical application, such as the unclear mechanisms of immune tolerance induction and the potential risk of increased infections or tumors with high doses of Tregs [4]. - The discoveries related to peripheral immune tolerance and cancer immunotherapy provide promising avenues for disease treatment and will further promote research in immune mechanisms and therapies [4].