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.
These studies are relevant to the overall mission of the ACE which is to further our understanding of cellmediated autoimmunity. In particular, Th17 cells are a recently characterised cellular subset that have been implicated in a numer of autoimmune conditions. Thus, although our studies are focused on MS, the findings from this project will likely be relevant to a range of autoimmune conditions.
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