Norepinephrine promotes activated B cells to identify and kill effector CD8+ T cells through FasL/Fas pathway in spleen mononuclear cells isolated from experimental autoimmune encephalomyelitis.

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It has been reported that the nervous system can regulate immune reactions through various mechanisms. However, the role of splenic sympathetic nerve activity in the autoimmune reactions during the pathogenesis of experimental autoimmune encephalomyelitis (EAE) remained unclear. Here, we blocked the activity of the splenic sympathetic nerve and found that the number of adaptive immune cells, such as CD4+ T cells, CD8+ T cells and B cells, were upregulated. Additionally, there was an increase in the secretion of inflammatory cytokines in the spleen, and the neurological symptoms of EAE were exacerbated. In vitro experiments, we found that norepinephrine (NE), the neurotransmitter of the splenic sympathetic nerve, indirectly drove the death of effector CD8+ T cells. Furthermore, activated B cells, under the influence of NE, specifically recognized effector CD8+ T cells by upregulating MHC-I molecules and killed these cells via the FasL/Fas pathway. Our findings provide a new perspective on B cells killing effect in vitro, which was boosted by NE and demonstrate that the splenic sympathetic nerve controls the degree of autoimmune responses in EAE. This adds a new dimension to the diversity of NE's regulatory effects on adaptive immune cells and suggests a potential new therapeutic approach for autoimmune diseases.