Interactions between immune effector cells of the central nervous system appear to directly or indirectly influence the progress/regression of multiple sclerosis (MS). Here, we report that glial STAT1 and a '3 are distinctively phosphorylated following the interaction of activated lymphocytes and glia, and this effect is significantly inhibited by glatiramer acetate (GA), a disease-modifying drug for MS. GA also reduces the activations of STAT1 and a '3 by MS-Associated stimuli such as IFNI 3 or LPS in primary glia, but not neurons. Experiments in IFNI 3-And IFNI 3 receptor-deficient mice revealed that GA-induced inhibitions of STAT signaling are independent of IFNI 3 and its receptor. Interestingly, GA induces the expression levels of suppressor of cytokine signaling-1 and a '3, representative negative regulators of STAT signaling in glia. We further found that GA attenuates the LPS-Triggered enhancement of IL-2, a highly produced cytokine in patients with active MS, in CD4 + T cells co-cultured with glia, but not in CD4 + T cells alone. Collectively, these results provide that activation of glial STATs is an essential event in the interaction between glia and T cells, which is a possible underlying mechanism of GA action in MS. These findings provide an insight for the development of targeted therapies against MS.
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