Glatiramer acetate attenuates the activation of CD4 + T cells by modulating STAT1 and â'3 signaling in glia

Ye Hyeon Ahn, Sae Bom Jeon, Chi Young Chang, Eun Ah Goh, Sang Soo Kim, Ho Jin Kim, Jaewhan Song, Eun Jung Park

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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 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.

Original languageEnglish
Article number40484
JournalScientific reports
Volume7
DOIs
Publication statusPublished - 2017 Jan 17

All Science Journal Classification (ASJC) codes

  • General

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    Ahn, Y. H., Jeon, S. B., Chang, C. Y., Goh, E. A., Kim, S. S., Kim, H. J., Song, J., & Park, E. J. (2017). Glatiramer acetate attenuates the activation of CD4 + T cells by modulating STAT1 and â'3 signaling in glia. Scientific reports, 7, [40484]. https://doi.org/10.1038/srep40484