有证据表明，免疫衰老的过程是导致自身免疫性疾病的机制。随着年龄增长，免疫系统逐渐适应造血和淋巴发生的深刻变化，并在不断扩大的环境暴露面前逐渐重组。老年人的免疫系统无法产生足够的免疫应答来对抗微生物感染和肿瘤，但会积累老化的T细胞、B细胞和髓系细胞。与年龄相关的B细胞在产生自身抗体方面非常高效。T细胞衰老促进了末分化效应T细胞的积累，这些细胞具有强大的细胞毒性和促炎能力，而髓系细胞衰老则支持低程度、无菌和慢性炎症状态（炎症老化）。在易感个体中，免疫衰老可能导致明显的自身免疫疾病，表现为慢性炎症和不可逆转的组织损伤。新出现的数据支持这样一个概念，即自身免疫疾病是由于免疫效应细胞中基本细胞过程失效所引起的免疫衰老：基因组不稳定性、线粒体健康丧失、蛋白质稳态失调、溶酶体降解减少和自噬效率下降。在本文中，我们回顾了线粒体功能异常、溶酶体功能障碍和内质网应激诱导的发病性T细胞和巨细胞动脉炎的病理性巨噬细胞，这两种细胞驱动两种自身免疫疾病，即类风湿性关节炎（RA）和巨细胞动脉炎（GCA）。认识免疫衰老作为自身免疫疾病风险因素将开辟免疫调控疗法的新途径，包括修复功能失调的线粒体和溶酶体。 版权所有 © 2023 Elsevier Ltd. 发表。

Evidence is emerging that the process of immune aging is a mechanism leading to autoimmunity. Over lifetime, the immune system adapts to profound changes in hematopoiesis and lymphogenesis, and progressively restructures in face of an ever-expanding exposome. Older adults fail to generate adequate immune responses against microbial infections and tumors, but accumulate aged T cells, B cells and myeloid cells. Age-associated B cells are highly efficient in autoantibody production. T-cell aging promotes the accrual of end-differentiated effector T cells with potent cytotoxic and pro-inflammatory abilities and myeloid cell aging supports a low grade, sterile and chronic inflammatory state (inflammaging). In pre-disposed individuals, immune aging can lead to frank autoimmune disease, manifesting with chronic inflammation and irreversible tissue damage. Emerging data support the concept that autoimmunity results from aging-induced failure of fundamental cellular processes in immune effector cells: genomic instability, loss of mitochondrial fitness, failing proteostasis, dwindling lysosomal degradation and inefficient autophagy. Here, we have reviewed the evidence that malfunctional mitochondria, disabled lysosomes and stressed endoplasmic reticula induce pathogenic T cells and macrophages that drive two autoimmune diseases, rheumatoid arthritis (RA) and giant cell arteritis (GCA). Recognizing immune aging as a risk factor for autoimmunity will open new avenues of immunomodulatory therapy, including the repair of malfunctioning mitochondria and lysosomes.Copyright © 2023. Published by Elsevier Ltd.