Resolvin E1 Regulates Th17 Function and T Cell Activation

Abstract

Resolvin E1 (RvE1) is a specialized pro-resolving lipid mediator derived from eicosapentaenoic acid and plays a critical role in resolving inflammation and tissue homeostasis. T(h)17 cells are a distinct group of T helper (T-h) cells with tissue-destructive functions in autoimmune and chronic inflammatory diseases via the secretion of IL-17. Dendritic cell (DC)-mediated antigen presentation regulates the T(h)17-induced progression of inflammation and tissue destruction. In this study, we hypothesized that the RvE1 would restore homeostatic balance and inflammation by targeting the T(h)17 function. We designed three experiments to investigate the impact of RvE1 on different phases of T(h)17 response and the potential role of DCs: First CD4(+) T cells were induced by IL-6/TGF(beta) to measure the effect of RvE1 on T(h)17 differentiation in an inflammatory milieu. Second, we measured the impact of RvE1 on DC-stimulated T(h)17 differentiation in a co-culture model. Third, we measured the effect of RvE1 on DC maturation. RvE1 blocked the CD25, CCR6 and IL-17 expression; IL-17, IL-21, IL-10, and IL-2 production, suggesting inhibition of T cell activation, T(h)17 stimulation and chemoattraction. RvE1 also suppressed the activation of DCs by limiting their pro-inflammatory cytokine production. Our findings collectively demonstrated that the RvE1 targeted the T(h)17 activation and the DC function as a potential mechanism for inflammatory resolution and acquired immune response.