Metabolic abnormalities and oxidative stress in lupus.
Metabolic abnormalities and oxidative stress in lupus.
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DOI：
10.1097/bor.0000000000000413
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发表时间：
2017-09
影响因子：
5.1
通讯作者：
Kaplan MJ
中科院分区：
文献类型：
--
作者：
Lightfoot YL;Blanco LP;Kaplan MJ
在抗原暴露后，免疫细胞依赖于细胞特异性代谢途径来产生有效的免疫应答。在自身免疫中，关键代谢检查点的失败可能导致免疫细胞过度活化和组织损伤。自身免疫患者的氧化应激也可导致免疫失调和对宿主的损伤。本文讨论了与系统性红斑狼疮（SLE）特异性相关的免疫细胞代谢特征以及患者氧化应激升高的后果。葡萄糖代谢抑制剂、mTOR通路调节剂和PPARγ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似乎是有害的狼疮。目前正在测试针对狼疮免疫细胞中代谢失衡的重新配置和线粒体ROS产生/可用性的减少而定制的有效疗法。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，目前还缺乏相关知识。尽管如此，SLE特异性代谢特征已经被鉴定，并且它们的特异性靶向，沿着线粒体ROS抑制剂/清除剂，可以在狼疮患者中显示治疗优势。
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 hyper-activation 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, mTOR pathway modulators, and PPARγ-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 towards 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.