The cysteinyl leukotriene receptor CysLTR1 mediates Th17 cell migration (CAM4P.156)

Abstract

Abstract Th17 cells are one of CD4+ T cells that have crucial role in inflammation and autoimmunity. Although many studies revealed molecular mechanisms about Th17 cells but the migration of Th17 cells by lipid-based chemoattractant leukotriene signaling is not fully understood. Here, we show that Th17 cells are highly sensitive to leukotriene B4 and D4. Th17 cells expressed high levels of leukotriene B4 receptors and cysteinyl leukotriene receptors compare to other effector CD4+ T cell subsets. In chemotaxis assay, we confirmed that migration of Th17 cells was more efficient than that of other effector T CD4+ T cell subsets under the guidance of leukotriene B4 and D4, and it was blocked by specific inhibitors of leukotriene B4 receptor and cysteinyl leukotriene receptor. Finally in an animal disease model of experimental autoimmune encephalomyelitis (EAE), treatment with montelukast which is an inhibitor of cysteinyl leukotriene receptor, it mitigated clinical score of EAE. Thus, we concluded that leukotrienes act as chemoattractant for Th17 cells.