서강대학교

초록/요약

T helper 17 (Th17) cells are one of CD4+ T cells that produce IL-17A, IL-17F, and IL-22 cytokines to mediate pathogen clearance and host protection whereas play a crucial role in autoimmunity. Th17 cells are differentiated from naïve CD4+ T cells by differentiation signals such as IL-6 and TGF-β and migrate to the infection site to mediate inflammatory responses. However, the specific mechanisms that regulate migration and differentiation of Th17 cells not been elucidated. In this study, I studied molecular mechanisms that regulate migration and differentiation of Th17 cells and showed that Cysteinyl leukotriene receptor 1 (CysLTR1) regulates the migration of Th17 cells whereas Phosphatase and tensin homologue (PTEN) regulates the differentiation of Th17 cells. CysLTR1 mediates Th17 cell migration by recognizing leukotriene D4, which is expressed in inflamed tissue, and PTEN suppresses IL-2 cytokine, which inhibits Th17 cell differentiation, through PI(3)K/AKT signaling cascade. Additionally, I induced experimental autoimmune encephalomyelitis (EAE) to mice and then treated inhibitor of CysLTR1 (Montelukast) and PTEN (SF1670) respectively. Each inhibitor treatment ameliorated the symptoms of EAE. Taken together, I demonstrated the effect of CysLTR1 and PTEN on migration and differentiation of Th17 cells and showed the possibility that those molecules could be used as the therapeutic targets to cure autoimmune diseases which are mediated by Th17 cells.