Kwong Chun-Ting J, Kaplan Mariana J
Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, 10 Center Drive, 12N248C, Bethesda, MD 20892, USA.
Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, 10 Center Drive, 12N248C, Bethesda, MD 20892, USA.
Trends Immunol. 2025 Sep 9. doi: 10.1016/j.it.2025.08.003.
Autoimmune diseases arise from genetic and environmental factors that disrupt immune tolerance. Recent studies highlight the role of myeloid cell immunometabolism, particularly mitochondrial dysfunction, in driving autoimmunity. Mitochondria regulate energy homeostasis and cell fate; their impairment leads to defective immune cell differentiation, abnormal effector activity, and chronic inflammation. We propose that chronic metabolic stress reprograms myeloid cells, fueling a vicious cycle of cell death and immune activation. Over time, this may induce several states of maladaptation in myeloid cells. Viewing autoimmune disease through a metabolic lens offers new insight into disease mechanisms and highlights potential therapeutic opportunities targeting mitochondrial function to restore immune balance.
自身免疫性疾病源于破坏免疫耐受的遗传和环境因素。最近的研究强调了髓系细胞免疫代谢，特别是线粒体功能障碍在驱动自身免疫中的作用。线粒体调节能量稳态和细胞命运；它们的损伤导致免疫细胞分化缺陷、效应器活性异常和慢性炎症。我们提出，慢性代谢应激会使髓系细胞重编程，加剧细胞死亡和免疫激活的恶性循环。随着时间的推移，这可能会在髓系细胞中诱导几种适应不良状态。从代谢角度看待自身免疫性疾病为疾病机制提供了新的见解，并突出了针对线粒体功能以恢复免疫平衡的潜在治疗机会。
