Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida 32610, USA.
Nat Rev Rheumatol. 2017 May;13(5):280-290. doi: 10.1038/nrrheum.2017.43. Epub 2017 Mar 31.
Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by pathogenic autoantibodies directed against nucleoprotein complexes. Beyond the activation of autoreactive B cells, this process involves dysregulation in many other types of immune cells, including CD4 T cells, dendritic cells, macrophages and neutrophils. Metabolic substrate utilization and integration of cues from energy sensors are critical checkpoints of effector functions in the immune system, with common as well as cell-specific programmes. Patients with SLE and lupus-prone mice present with activated metabolism of CD4 T cells, and the use of metabolic inhibitors to normalize these features is associated with therapeutic effects. Far less is known about the metabolic requirements of B cells and myeloid cells in SLE. This article reviews current knowledge of the alterations in metabolism of immune cells in patients with SLE and mouse models of lupus in the context of what is known about the metabolic regulation of these cells during normal immune responses. How these alterations might contribute to lupus pathogenesis and how they can be targeted therapeutically are also discussed.
系统性红斑狼疮(SLE)是一种自身免疫性疾病,由针对核蛋白复合物的致病性自身抗体介导。除了自身反应性 B 细胞的激活外,该过程还涉及许多其他类型的免疫细胞的失调,包括 CD4 T 细胞、树突状细胞、巨噬细胞和中性粒细胞。代谢底物的利用和能量传感器信号的整合是免疫系统效应功能的关键检查点,存在共同的和细胞特异性的程序。SLE 患者和狼疮易感小鼠的 CD4 T 细胞表现出代谢激活,使用代谢抑制剂使这些特征正常化与治疗效果相关。关于 SLE 患者 B 细胞和髓样细胞的代谢需求知之甚少。本文综述了 SLE 患者和狼疮小鼠模型中免疫细胞代谢改变的最新知识,并结合了正常免疫反应中这些细胞代谢调节的知识。这些改变如何促进狼疮发病机制,以及如何进行治疗性靶向,也进行了讨论。