Regulatory Properties of Copolymer I in Th17 Differentiation by Altering STAT3 Phosphorylation

被引：18

作者：

Chen, Chunhua ^{[1
,2
]}

Liu, Xuebin ^{[3
]}

Wan, Bing ^{[3
]}

Zhang, Jingwu Z. ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai 200025, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Med, Shanghai 200030, Peoples R China

[3] GlaxoSmithKline Res & Dev Ctr, Dept Neuroinflammat, Shanghai, Peoples R China

来源：

JOURNAL OF IMMUNOLOGY | 2009年 / 183卷 / 01期

基金：

中国国家自然科学基金;

关键词：

EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; T-CELL POPULATION; MULTIPLE-SCLEROSIS; GLATIRAMER ACETATE; MECHANISMS; RESPONSES; INFLAMMATION; MICE; COPAXONE(R);

D O I：

10.4049/jimmunol.0900193

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 regulator, 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 ROR gamma t 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. The Journal of Immunology, 2009, 183: 246-253.

引用

页码：246 / 253

页数：8

共 38 条

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