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 language | English |
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Article number | 40484 |
Journal | Scientific reports |
Volume | 7 |
DOIs | |
Publication status | Published - 2017 Jan 17 |
Bibliographical note
Funding Information:We thank Dr. Sang Jin Lee and members of NCC animal core for expert assistance. We also thank all members of E.J. Park's laboratory, especially Ms. Mi Jeon Song, for their helpful comments and discussions. This work was supported by the National Cancer Center (1510080 to E.J.P) and National Research Foundation of Korea (NRF- 2014R1A2A2A01005064 to E.J.P). S.Jeon is supported by the program for next-generation researchers from NRF (2013R1A6A3A0162254).
All Science Journal Classification (ASJC) codes
- General