Department of Medicine, State University of New York Upstate Medical University, Syracuse, 13210, USA.
Clin Immunol. 2012 Sep;144(3):200-13. doi: 10.1016/j.clim.2012.07.001. Epub 2012 Jul 13.
Abnormal T-cell signaling and activation are characteristic features in systemic lupus erythematosus (SLE). Lupus T cells are shifted toward an over-activated state, important signaling pathways are rewired, and signaling molecules are replaced. Disturbances in metabolic and organelle homeostasis, importantly within the mitochondrial, endosomal, and autophagosomal compartments, underlie the changes in signal transduction. Mitochondrial hyperpolarization, enhanced endosomal recycling, and dysregulated autophagy are hallmarks of pathologic organelle homeostasis in SLE. This review is focused on the metabolic checkpoints of endosomal traffic that control immunological synapse formation and mitophagy and may thus serve as targets for treatment in SLE.
异常的 T 细胞信号转导和激活是系统性红斑狼疮(SLE)的特征。狼疮 T 细胞向过度激活状态转变,重要的信号通路被重新布线,信号分子被替换。代谢和细胞器内稳态的紊乱,特别是在线粒体、内体和自噬体 compartments 中,是信号转导变化的基础。线粒体超极化、增强的内体再循环和失调的自噬是 SLE 病理性细胞器内稳态的标志。这篇综述集中讨论了控制免疫突触形成和线粒体自噬的内体运输的代谢检查点,因此可能成为 SLE 治疗的靶点。