GSH-dependent regulation of IL-17-producing CD8+ T cells in autoimmune inflammation of the central nervous system

T细胞介导的中枢神经系统自身免疫（CNS）是由外周T细胞的激活启动的。随后，效应T细胞迁移到靶组织介导炎症。因此，改变早期T细胞激活的因素影响了随后的疾病爆发。抗原识别相关信号上调活性氧（ROS）的产生，干扰细胞反应。高浓度的ROS会导致死亡，而低浓度的ROS则支持T细胞活化，这表明ROS对活化结果有调节作用。最重要的细胞ROS清除剂是谷胱甘肽（GSH），它的丢失会损害T细胞的代谢重编程和扩张。然而，暂时GSH耗竭对T细胞命运的影响尚不清楚。富马酸二甲酯（DMF）是一种被批准用于治疗复发缓解型多发性硬化症（RRMS）的药物，RRMS是一种T细胞介导的中枢神经系统自身免疫性疾病，具有短暂的gsh消耗活性。考虑到DMF对T细胞的影响尚不完全清楚，我们试图描述gsh消耗对与ms相关的Tc17细胞命运的主要影响。这项研究将提供促氧化剂如何影响il -17驱动的自身免疫及其潜在影响的机制见解。

T cell-mediated autoimmunity of the central nervous system (CNS) is initiated by the activation of T cells in the periphery. Subsequently, the effector T cells migrate into the target tissue to mediate inflammation. Thus, factors modifying early T cell activation affect the following disease outbreak. Antigen recognition associated signaling upregulates reactive oxygen species (ROS) production, which interfere with cellular response. Whereas high ROS concentrations cause death, low levels support T cell activation, indicating modulating effect of ROS on the activation outcome. The most important cellular ROS scavenger is glutathione (GSH), which loss impairs T cell metabolic reprogramming and expansion. However, the influence of a transient GSH depletion on the T cell fate is not known. Dimethyl fumarate (DMF), a drug approved for treatment of relapsing remitting multiple sclerosis (RRMS), a T cell-mediated autoimmune disease of the CNS, has a transient GSH-depleting activity. Considering that effects of DMF on T cells are not exactly known, we seek to delineate the principal impact of GSH-depletion on the fate of Tc17 cells with relevance for MS. This investigation will give mechanistic insights how pro-oxidants impinge on IL-17-driven autoimmunity and potentially beyond.