Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Front Immunol. 2022 Jun 3;13:916664. doi: 10.3389/fimmu.2022.916664. eCollection 2022.
Adequate control of autoimmune diseases with an unclear etiology resulting from autoreactivation of the immune system remains a major challenge. One of the factors that trigger autoimmunity is the abnormal induction of cell death and the inadequate clearance of dead cells that leads to the exposure or release of intracellular contents that activate the immune system. Different from other cell death subtypes, such as apoptosis, necroptosis, autophagy, and pyroptosis, ferroptosis has a unique association with the cellular iron load (but not the loads of other metals) and preserves its distinguishable morphological, biological, and genetic features. This review addresses how ferroptosis is initiated and how it contributes to the pathogenesis of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel diseases. The mechanisms responsible for ferroptosis-associated events are discussed. We also cover the perspective of targeting ferroptosis as a potential therapeutic for patients with autoimmune diseases. Collectively, this review provides up-to-date knowledge regarding how ferroptosis occurs and its significance in autoimmune diseases.
自身免疫性疾病的病因不明,其发病机制与免疫系统的自身激活有关,目前仍难以有效控制。导致自身免疫的因素之一是细胞死亡的异常诱导和死亡细胞的清除不足,导致细胞内物质的暴露或释放,从而激活免疫系统。与其他细胞死亡亚型(如凋亡、坏死、自噬和细胞焦亡)不同,铁死亡与细胞内铁负荷(而不是其他金属的负荷)有独特的关联,并保持其可区分的形态、生物和遗传特征。本综述讨论了铁死亡的发生机制以及其在自身免疫性疾病发病机制中的作用,包括系统性红斑狼疮、类风湿关节炎和炎症性肠病。讨论了与铁死亡相关事件相关的机制。我们还涵盖了将铁死亡作为自身免疫性疾病患者潜在治疗靶点的观点。总的来说,本综述提供了关于铁死亡发生及其在自身免疫性疾病中的意义的最新知识。