Investigation of Th 17 cells in Multiple Sclerosis

Th 17细胞是一种新定义的辅助性T细胞亚群，可协调炎症反应。 越来越多的证据表明Th 17细胞参与了自身免疫性疾病的发病机制。间接证据 表明它们在多发性硬化症（MS）的发病机制中也很重要。但没有 对人类的研究证实了这一假设。 Th 17细胞在实验性自身免疫性脑脊髓炎中是致病性的，我们已经证明IL-27 抑制Th 17细胞和自身免疫性炎症。此外，IFN-β是一种免疫调节治疗剂， 对于MS，已显示通过上调 IL-27。 基于这些观察结果，我们假设Th 17细胞在MS中起致病作用，并且可以通过免疫调节作用来调节。 被IFN-|为了验证这一假设，我们提出1）表征MS中的Th 17细胞， 2）确定IL-27对人Th 17细胞的作用，和3）检查IL-27在人Th 17细胞中的作用。 IFN-β对Th 17细胞的抑制作用。 这些研究将有助于更好地理解Th 17细胞在MS中的作用，阐明其在MS中的作用。 IFN-P在这种疾病中的作用机制，并有可能引入IL-27作为治疗剂 人类自身免疫性炎症的模式。

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.