Glatiramer acetate attenuates the activation of CD4⁺ T cells by modulating STAT1 and -3 signaling in glia.

ABSTRACT: 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 -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 -3 by MS-associated stimuli such as IFN? or LPS in primary glia, but not neurons. Experiments in IFN?- and IFN? receptor-deficient mice revealed that GA-induced inhibitions of STAT signaling are independent of IFN? and its receptor. Interestingly, GA induces the expression levels of suppressor of cytokine signaling-1 and -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.

SUBMITTER: Ahn YH 

PROVIDER: S-EPMC5240344 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature