Regulatory properties of copolymer I in Th17 differentiation by altering STAT3 phosphorylation.

Chunhua Chen, Xuebin Liu, Bing Wan, Jingwu Z Zhang

Institute of Health Sciences, Shanghai JiaoTong University School of Medicine, China.

Journal of immunology (Baltimore, Md. : 1950) 2009 Jul 1

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Th17 and Th1 play an important role in multiple sclerosis for which copolymer I (COP-I) is a treatment option. We described here that the treatment effect of COP-I correlated with its unique regulatory properties on differentiation and survival of Th17 in experimental autoimmune encephalomyelitis mice, which was mediated through down-regulation of STAT3 phosphorylation. The effect of COP-I on Th17 differentiation required CD14(+) monocytes through IL-6 signaling as a key mediator to regulate STAT3 phosphorylation and subsequent RORgammat expression in Th17 cells. The observed effect was markedly dampened when monocytes were genetically deficient for IL-6. Similar regulatory properties of COP-I were demonstrated in human Th17 differentiation. The study revealed the differential regulatory roles and the novel mechanism of action of COP-I chiefly responsible for its treatment efficacy in experimental autoimmune encephalomyelitis and multiple sclerosis.

Citation

Chunhua Chen, Xuebin Liu, Bing Wan, Jingwu Z Zhang. Regulatory properties of copolymer I in Th17 differentiation by altering STAT3 phosphorylation. Journal of immunology (Baltimore, Md. : 1950). 2009 Jul 1;183(1):246-53