Hu Huifang, Zhang Guangyue, Chen Tao, Liu Yi, Meng Liesu, Holmdahl Rikard, Dai Lunzhi, Zhao Yi
Department of Rheumatology and Immunology, West China Hospital, Sichuan University, 610041 Chengdu, Sichuan, China; Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, 610041 Chengdu, Sichuan, China.
Department of Rheumatology, and National Joint Engineering Research Center of Biodiagnostics and Biotherapy, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, PR China.
Autoimmun Rev. 2025 May 30;24(6):103805. doi: 10.1016/j.autrev.2025.103805. Epub 2025 Mar 23.
Autoimmune diseases (AIDs) are a group of disorders in which the immune system mistakenly attacks the body's own tissues, characterized by the loss of tolerance to self-antigens and destruction of tissues. Aging is a natural process of physiological decline that also alters the immune system, a condition known as immunosenescence. During immunosenescence, the immune system undergoes various changes, including modifications and antigenicity of self-antigens, abnormalities in the quantity, phenotype, and function of lymphocytes and antibodies, as well as a narrowing of the B and T cell receptor repertoire, changes that may increase susceptibility to AIDs. Additionally, senescent immune cells and the senescence-associated secretory phenotype (SASP) contribute to target organ involvement in AIDs, exacerbating chronic inflammation and tissue damage. Mitochondrial dysfunction and metabolic imbalances in AIDs lead to the accumulation of senescent cells, which act as upstream drivers of immunosenescence. In this review, we summarize the bidirectional relationship between AIDs and immunosenescence, as well as its potential mechanisms. Therapeutic approaches targeting immunosenescence in AIDs remain at an early stage. Strategies aimed at resetting or reversing the aging immune system are expected to become a novel direction in the future.
自身免疫性疾病（AIDs）是一组免疫系统错误攻击人体自身组织的疾病，其特征是对自身抗原失去耐受性并导致组织破坏。衰老是一种生理功能衰退的自然过程，它也会改变免疫系统，这种情况被称为免疫衰老。在免疫衰老过程中，免疫系统会发生各种变化，包括自身抗原的修饰和抗原性、淋巴细胞和抗体数量、表型及功能的异常，以及B细胞和T细胞受体库的缩小，这些变化可能会增加患自身免疫性疾病的易感性。此外，衰老的免疫细胞和衰老相关分泌表型（SASP）会导致自身免疫性疾病中的靶器官受累，加剧慢性炎症和组织损伤。自身免疫性疾病中的线粒体功能障碍和代谢失衡会导致衰老细胞的积累，而衰老细胞是免疫衰老的上游驱动因素。在本综述中，我们总结了自身免疫性疾病与免疫衰老之间的双向关系及其潜在机制。针对自身免疫性疾病中免疫衰老的治疗方法仍处于早期阶段。旨在重置或逆转衰老免疫系统的策略有望成为未来的一个新方向。
