Investigation of Th 17 cells in Multiple Sclerosis

Th17细胞是一个新定义的辅助性T细胞亚群，负责协调炎症反应。 越来越多的证据表明Th17细胞与自身免疫性疾病的发病机制有关。间接证据 提示它们在多发性硬化症(MS)的发病机制中也很重要。然而，没有 对人类的研究证实了这一假设。 Th17细胞在实验性自身免疫性脑脊髓炎中是致病的，我们已经证明IL-27 抑制Th17细胞和自身免疫性炎症。此外，干扰素-(3)是一种免疫调节治疗 对于多发性硬化症，已被证明抑制Th17细胞和小鼠的自身免疫性炎症，通过上调 IL-27。 基于这些观察，我们假设Th17细胞在MS中起致病作用，并且可能是 被干扰素-3和IL-27抑制。为了验证这一假说，我们建议1)表征MS患者的Th17细胞 患者，2)确定IL-27对人Th17细胞的影响，以及3)检测IL-27在 干扰素-β对Th17细胞的抑制作用。 这些研究应该有助于更好地理解Th17细胞在多发性硬化中的作用，阐明 干扰素-P在本病中的作用机制，并有可能引入IL-27作为治疗手段 人类自身免疫性炎症的方式。

Th17 cells are a newly defined subset of helper T cells that orchestrate inflammatory responses. Accumulating evidence implicates Th17 cells in the pathogenesis of autoimmune diseases. Indirect evidence suggests that they are also important in the pathogenesis of multiple sclerosis (MS). However, there are no studies in man to confirm this hypothesis. Th17 cells are pathogenic in experimental autoimmune encephalomyelitis and we have shown that IL-27 suppresses Th17 cells and autoimmune inflammation. Furthermore, IFN-(3 an immunomodulatory treatment for MS, has been shown to suppress Th17 cells and autoimmune inflammation in mice, via upregulation of IL-27. Based on these observations, we hypothesize that Th17 cells play a pathogenic role in MS and can be suppressed by IFN-|3 and IL27.To test this hypothesis, we propose to 1) characterize Th17 cells in MS patients, 2) determine the effect of IL-27 on human Th17 cells, and 3) examine the role of IL-27 in the suppressive effect of IFN-p on Th17 cells. These studies should result in a better understanding of the role of Th17 cells in MS , elucidate a mechanism of action of IFN-P in this disease, and have the potential to introduce IL-27 as a therapeutic modality in human autoimmune inflammation.