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

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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.