307 Identification of resolvin E1, an omega-3 poly-unsaturated fatty acids-derived lipid mediator, as an inhibitor for psoriatic dermatitis by downregulating migration of IL-17A-producing cutaneous γδ T cells and IL-23 production from dendritic cells

Abstract

The potential of omega-3 poly-unsaturated fatty acids (PUFAs) as a therapeutic target for psoriasis is a long-disputed question, since various epidemiological studies have suggested that intake of omega-3 PUFAs have ameliorating effect on the development of psoriasis. However, its actual significance and the molecular mechanisms have not been explored. In this study, we examined the effect of resolvin E1 (RvE1), a metabolite derived from omega-3 PUFAs, on psoriatic dermatitis using an imiquimod-induced mouse psoriasis model. RvE1 potently suppressed the inflammatory cell infiltration and epidermal hyperplasia in the psoriatic skin. In addition, RvE1 decreased the mRNA expression of key cytokines including IL-23 and IL-17A, which are produced by cutaneous dendritic cells (DCs) and γδ T cells, respectively. Consistently, RvE1 inhibited IL-23p19 and IL-23p40 mRNA expression in bone marrow-derived DCs in vitro. Furthermore, an in vivo cell migration assay using Kaede (a photo-convertible protein)-transgenic mice revealed that RvE1 significantly inhibited migration of both cutaneous DCs and γδ T cells from skin to draining lymph nodes (dLNs), an essential step for γδ T cell expansion in dLNs and their subsequent recirculation into skin to accelerate the psoriatic dermatitis. We have also revealed that this suppressive effect of RvE1 on γδ T cell migration was mediated by RvE1’s antagonistic function on BLT1, a receptor of leukotriene B4. Taken together, these results indicate that RvE1 exerts anti-inflammatory effects on psoriatic dermatitis in two manners; the attenuation of γδ T cell migration from skin to dLNs and the inhibition of IL-23 production from DCs. Our results have clarified a novel mechanism of omega-3 PUFA-mediated amelioration of psoriasis, and suggest a potential of RvE1 as a therapeutic target for psoriasis.