Rheumatology Section, Universidad de Antioquia, Medellín, Colombia.
Grupo de Inmunología Celular e Inmunogenética, Universidad de Antioquia, Medellín, Colombia.
Immunopharmacol Immunotoxicol. 2022 Aug;44(4):457-470. doi: 10.1080/08923973.2022.2055568. Epub 2022 Mar 30.
In the immunopathogenesis of systemic lupus erythematosus (SLE), there is a dysregulation of specific immune cells, including T cells. The metabolic reprogramming in T cells causes different effects. Metabolic programs are critical checkpoints in immune responses and are involved in the etiology of autoimmune disease. For instance, resting lymphocytes generate energy through oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO), whereas activated lymphocytes rapidly shift to the glycolytic pathway. Specifically, mitochondrial dysfunction, oxidative stress, abnormal metabolism (including glucose, lipid, and amino acid metabolism), and mTOR signaling are hallmarks of T lymphocyte metabolic dysfunction in SLE. Herein it is summarized how metabolic defects contribute to T cell responses in SLE, and some epigenetic alterations involved in the disease. Finally, it is shown how metabolic defects could be modified therapeutically.
在系统性红斑狼疮(SLE)的免疫发病机制中,存在特定免疫细胞(包括 T 细胞)的失调。T 细胞的代谢重编程会产生不同的影响。代谢程序是免疫反应的关键检查点,并且参与自身免疫性疾病的发病机制。例如,静止的淋巴细胞通过氧化磷酸化(OXPHOS)和脂肪酸氧化(FAO)产生能量,而激活的淋巴细胞则迅速转向糖酵解途径。具体而言,线粒体功能障碍、氧化应激、异常代谢(包括葡萄糖、脂质和氨基酸代谢)以及 mTOR 信号是 SLE 中 T 淋巴细胞代谢功能障碍的标志。本文总结了代谢缺陷如何促进 SLE 中的 T 细胞反应,以及疾病中涉及的一些表观遗传改变。最后,展示了如何在治疗上修饰代谢缺陷。