Patiño-Martinez Eduardo, Kaplan Mariana J
Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Nat Rev Rheumatol. 2025 Jun 16. doi: 10.1038/s41584-025-01267-0.
Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by chronic inflammation, tissue damage, accelerated cardiovascular disease and the synthesis of autoantibodies that target nucleic acids and nuclear protein complexes. Emerging evidence underscores the key role of immune metabolic dysregulation in SLE, revealing how metabolic reprogramming during immune cell activation influences disease development and progression. Alterations in key metabolic pathways such as glycolysis and oxidative phosphorylation profoundly affect the activation, differentiation and function of B and T cells, monocytes, neutrophils and other immune cells, driving inflammation and tissue injury. This Review synthesizes current findings on immune cell metabolism in animal models of lupus and in patients with SLE, highlighting the interplay of metabolic disturbances, mitochondrial dysfunction and disease pathogenesis. Furthermore, it explores the potential of targeting metabolic pathways as therapeutic strategies to mitigate organ damage and improve outcomes in SLE.
系统性红斑狼疮(SLE)是一种多方面的自身免疫性疾病,其特征为慢性炎症、组织损伤、心血管疾病加速以及针对核酸和核蛋白复合物的自身抗体合成。新出现的证据强调了免疫代谢失调在SLE中的关键作用,揭示了免疫细胞激活过程中的代谢重编程如何影响疾病的发展和进程。糖酵解和氧化磷酸化等关键代谢途径的改变深刻影响B细胞、T细胞、单核细胞、中性粒细胞和其他免疫细胞的激活、分化和功能,从而引发炎症和组织损伤。本综述综合了狼疮动物模型和SLE患者中免疫细胞代谢的当前研究结果,突出了代谢紊乱、线粒体功能障碍与疾病发病机制之间的相互作用。此外,还探讨了将代谢途径作为治疗策略以减轻SLE器官损伤并改善预后的潜力。