Lightfoot Yaima L, Blanco Luz P, Kaplan Mariana J
Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Curr Opin Rheumatol. 2017 Sep;29(5):442-449. doi: 10.1097/BOR.0000000000000413.
Upon antigen exposure, immune cells rely on cell-specific metabolic pathways to mount an efficient immune response. In autoimmunity, failure in critical metabolic checkpoints may lead to immune cell hyperactivation and tissue damage. Oxidative stress in autoimmune patients can also contribute to immune dysregulation and injury to the host. Recent insights into the immune cell metabolism signatures, specifically associated with systemic lupus erythematosus (SLE) and the consequences of heightened oxidative stress in patients, are discussed herein.
Glucose metabolism inhibitors, mechanistic target of rapamycin pathway modulators, and peroxisome proliferator-activated receptor gamma-activating compounds demonstrate therapeutic benefit in experimental models of lupus. Mitochondrial-derived reactive oxygen species (ROS) and molecular modifications induced by oxidative stress appear to be detrimental in lupus. Effective therapies tailored toward the reconfiguration of metabolic imbalances in lupus immune cells and the reduction of mitochondrial ROS production/availability are currently being tested.
A paucity of knowledge exists regarding the metabolic needs of a number of immune cells involved in the pathogenesis of SLE, including myeloid cells and B cells. Nonetheless, SLE-specific metabolic signatures have been identified and their specific targeting, along with mitochondrial ROS inhibitors/scavengers, could show therapeutic advantage in lupus patients.
免疫细胞在接触抗原后，依靠细胞特异性代谢途径来产生有效的免疫反应。在自身免疫中，关键代谢检查点的失效可能导致免疫细胞过度激活和组织损伤。自身免疫患者的氧化应激也可能导致免疫失调和宿主损伤。本文讨论了对免疫细胞代谢特征的最新见解，特别是与系统性红斑狼疮（SLE）相关的特征以及患者氧化应激加剧的后果。
葡萄糖代谢抑制剂、雷帕霉素机制性靶标途径调节剂和过氧化物酶体增殖物激活受体γ激活化合物在狼疮实验模型中显示出治疗益处。线粒体衍生的活性氧（ROS）和氧化应激诱导的分子修饰在狼疮中似乎是有害的。目前正在测试针对狼疮免疫细胞代谢失衡的重新配置和线粒体ROS产生/可用性降低的有效疗法。
关于参与SLE发病机制的许多免疫细胞（包括髓样细胞和B细胞）的代谢需求，目前了解较少。尽管如此，已经确定了SLE特异性代谢特征，对其进行特异性靶向治疗，以及使用线粒体ROS抑制剂/清除剂，可能对狼疮患者显示出治疗优势。
