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_h17 cells are a distinct group of T helper (T_h) cells with tissue-destructive functions in autoimmune and chronic inflammatory diseases <i>via</i> the secretion of IL-17. Dendritic cell (DC)-mediated antigen presentation regulates the T_h17-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_h17 function. We designed three experiments to investigate the impact of RvE1 on different phases of T_h17 response and the potential role of DCs: First CD4⁺ T cells were induced by IL-6/TGF_β to measure the effect of RvE1 on T_h17 differentiation in an inflammatory milieu. Second, we measured the impact of RvE1 on DC-stimulated T_h17 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_h17 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_h17 activation and the DC function as a potential mechanism for inflammatory resolution and acquired immune response.