Novel Function of Extracellular Matrix Protein 1 in Suppressing Th17 Cell Development in Experimental Autoimmune Encephalomyelitis.
Novel Function of Extracellular Matrix Protein 1 in Suppressing Th17 Cell Development in Experimental Autoimmune Encephalomyelitis.
复制标题
细胞外基质蛋白1在抑制实验性自身免疫性脑脊髓炎中抑制Th17细胞发育中的新功能。
DOI：
10.4049/jimmunol.1502457
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发表时间：
2016-08-15
期刊：
影响因子：
--
通讯作者：
Sun B
中科院分区：
文献类型：
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作者：
Su P;Chen S;Zheng YH;Zhou HY;Yan CH;Yu F;Zhang YG;He L;Zhang Y;Wang Y;Wu L;Wu X;Yu B;Ma LY;Yang Z;Wang J;Zhao G;Zhu J;Wu ZY;Sun B
多发性硬化症(MS)是一种以脱髓鞘和轴突损害为特征的慢性中枢神经系统炎症性疾病。实验性自身免疫性脑脊髓炎(EAE)是一种成熟的人类MS动物模型，Th17细胞在发病过程中起重要作用，而Th2细胞在这一过程中起抑制作用。在这里，我们报告了Th2细胞产物细胞外基质蛋白1(ECM1)对Th17细胞分化和实验性自身免疫性脑脊髓炎(EAE)发展的影响。我们的结果表明，在EAE诱导后的第1天到第7天给予ECM1可以改善Th17细胞的反应和体内EAE的发展。进一步的机制研究表明，ECM1可与DC细胞表面的αv整合素相互作用，阻断αv整合素介导的潜伏β的激活，从而在诱导早期抑制Th17的分化。此外，ECM1在体内的过表达显著抑制了ECM1转基因小鼠的Th17细胞反应和EAE诱导。总之，我们的工作发现了ECM1在EAE模型中抑制Th17分化的新功能，表明ECM1可能在了解MS的发病机制和诊断方面具有潜在的临床应用价值。
Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS characterized by demyelination and axonal damage. Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model for human MS. While Th17 cells are important for the disease induction, Th2 cells are inhibitory in this process. Here, we report the effect of a Th2 cell product, extracellular matrix protein 1 (ECM1), on the differentiation of Th17 cells and the development of experimental autoimmune encephalomyelitis (EAE). Our results demonstrated that ECM1 administration from day 1 to day 7 following the EAE induction could ameliorate the Th17 cell responses and EAE development in vivo. Further mechanism study revealed that ECM1 could interact with αv integrin on DC cells and block the αv integrin-mediated activation of latent TGF-β, resulting in an inhibition of Th17 differentiation at early stage of EAE induction. Furthermore, overexpression of ECM1 in vivo significantly inhibited Th17 cell response and EAE induction in ECM1 transgenic mouse. Overall, our work has identified a novel function of ECM1 in inhibiting Th17 differentiation in the EAE model, suggesting that ECM1 may have a potential to be used in clinical applications for understanding the pathogenesis of MS and its diagnosis.