Resolvin E1 attenuates murine psoriatic dermatitis

  • Sawada, Yu
    Department of Dermatology, Kyoto University Graduate School of Medicine・Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu
  • Honda, Tetsuya
    Department of Dermatology, Kyoto University Graduate School of Medicine
  • Nakamizo, Satoshi
    Department of Dermatology, Kyoto University Graduate School of Medicine
  • Otsuka, Atsushi
    Department of Dermatology, Kyoto University Graduate School of Medicine
  • Ogawa, Narihito
    Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology
  • Kobayashi, Yuichi
    Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology
  • Nakamura, Motonobu
    Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu
  • Kabashima, Kenji
    Department of Dermatology, Kyoto University Graduate School of Medicine・Singapore Immunology Network (SIgN) and Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR)

Abstract

The potential of omega-3 poly-unsaturated fatty acids (PUFAs) as a therapeutic target for psoriasis, a chronic inflammatory skin disease of IL-23/IL-17 axis, is a long-disputed question, since various epidemiological studies have suggested the association between high-intake of omega-3 PUFAs and the reduced frequency and severity of psoriasis. However, their actual significance and the molecular mechanisms remain largely unknown. To address these issues, we focused on resolvin E1 (RvE1), an omega-3 PUFAs-derived metabolite, and examined its effects on psoriatic dermatitis, using an imiquimod-induced mouse psoriasis model. RvE1 potently suppressed the inflammatory cell infiltration and epidermal hyperplasia in the psoriatic skin. RvE1 decreased the mRNA expression of IL-23 in the skin. Consistently, RvE1 inhibited IL-23 production by dendritic cells (DCs) in vitro. Furthermore, RvE1 exerted inhibitory effects on migration of cutaneous DCs and γδ T cells, a major IL-17-producing cell population in mouse, both in vivo and in vitro. These suppressive effects of RvE1 were mediated by its antagonistic function on BLT1, a receptor of leukotriene B4, and were also observed in human DCs, Th17 and Tc17 cells. Our results indicate a novel mechanism of omega-3 PUFA-mediated amelioration of psoriasis, and suggest a potential of RvE1 as a therapeutic target for psoriasis.

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