Yin Fei, He Yangfang, Li Jian, Gao Yuan
Department of Neurology, The Second Hospital of Jilin University, Changchun, China.
Department of Endocrinology and Metabolism, The Second Hospital of Jilin University, Changchun, China.
Front Immunol. 2025 Aug 7;16:1596686. doi: 10.3389/fimmu.2025.1596686. eCollection 2025.
The senescence of immune cells has also emerged as a key hallmark of immunological dysregulation and chronic inflammation in autoimmunity. Senescent immune cells are irreversibly arrested in the cell cycle, exhibit antimetabolic characteristics, and secrete pro-inflammatory mediators, all together disrupting immune homeostasis. T cells, B cells, and innate immune subsets, acquire a senescence-associated secretory phenotype (SASP), which initiates tissue damage and sustains continuous inflammation in autoimmune diseases. The accumulation of senescent immune cells undermines immune surveillance, disrupts self-tolerance mechanisms, and enhances autoantibody production, all of which contribute to the pathogenesis of autoimmune diseases, including type 1 diabetes (T1D), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Accumulating evidence reveals that metabolic stress, chronic DNA damage, and persistent antigenic exposure in inflammatory microenvironments induce immune cell senescence. Such senescent condition more aggressively promotes disease pathogenesis by compromising antigen presentation, disrupting cytokine signaling, and weakening the function of regulatory T cells (Tregs). Targets of senolytic drugs, SASP inhibitors, monoclonal antibodies (mAbs), and CAR T cell therapy currently have the potential to accelerate autoimmune pathology. These treatments would be directed specifically against the selective elimination or reprogramming of senescent cells to restore immune homeostasis. This review examines the mechanistic relationships between autoimmune development and immune cell senescence, as well as recent advancements in senescence-directed therapy. Understanding these pathways can provide new insights into autoimmune pathogenesis and inform future therapeutic approaches to immune cell aging.
免疫细胞衰老也已成为自身免疫中免疫失调和慢性炎症的关键标志。衰老的免疫细胞在细胞周期中不可逆地停滞，表现出抗代谢特征，并分泌促炎介质，共同破坏免疫稳态。T细胞、B细胞和固有免疫亚群获得衰老相关分泌表型（SASP），这在自身免疫性疾病中引发组织损伤并维持持续炎症。衰老免疫细胞的积累破坏免疫监视，扰乱自身耐受机制，并增强自身抗体产生，所有这些都促成自身免疫性疾病的发病机制，包括1型糖尿病（T1D）、系统性红斑狼疮（SLE）和类风湿性关节炎（RA）。越来越多的证据表明，炎症微环境中的代谢应激、慢性DNA损伤和持续抗原暴露会诱导免疫细胞衰老。这种衰老状态通过损害抗原呈递、扰乱细胞因子信号传导和削弱调节性T细胞（Tregs）的功能，更积极地促进疾病发病机制。衰老细胞裂解药物、SASP抑制剂、单克隆抗体（mAb）和嵌合抗原受体T细胞（CAR T）疗法的靶点目前有可能加速自身免疫病理过程。这些治疗将专门针对衰老细胞的选择性消除或重编程，以恢复免疫稳态。本综述探讨了自身免疫发展与免疫细胞衰老之间的机制关系，以及衰老导向治疗的最新进展。了解这些途径可为自身免疫发病机制提供新见解，并为免疫细胞衰老的未来治疗方法提供参考。
