title: Dietary ω3 fatty acid exerts anti-allergic effect through the conversion to 17,18-epoxyeicosatetraenoic acid in the gut.
abstract: ω3 polyunsaturated fatty acids (PUFAs) have anti-allergic and anti-inflammatory properties, but the immune-metabolic progression from dietary oil remains to be investigated. Here we identified 17,18-epoxyeicostetraenoic acid (17,18-EpETE) as an anti-allergic metabolite generated in the gut from dietary ω3 α-linolenic acid (ALA). Biochemical and imaging mass spectrometry analyses revealed increased ALA and its metabolites, especially eicosapentaenoic acid (EPA), in the intestines of mice receiving ALA-rich linseed oil (Lin-mice). In murine food allergy model, the decreased incidence of allergic diarrhea in Lin-mice was due to impairment of mast cell degranulation without affecting allergen-specific serum IgE. Liquid chromatography-tandem mass spectrometry-based mediator lipidomics identified 17,18-EpETE as a major ω3 EPA-derived metabolite generated from dietary ALA in the gut, and 17,18-EpETE exhibits anti-allergic function when administered in vivo. These findings suggest that metabolizing dietary ω3 PUFAs generates 17,18-EpETE, which is an endogenous anti-allergic metabolite and potentially is a therapeutic target to control intestinal allergies.
authors.affiliation: 1] Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan [2] Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan [3] International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan [4] Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo 102-0075, Japan [5] Kobe University Graduate School of Medicine, Hyogo 650-0017, Japan [6] Graduate School of Medicine, Graduate School of Pharmaceutical Sciences, and Graduate School of Dentistry, Osaka University, Osaka 565-0871, Japan [7] Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan [8] Graduate School of Dentistry, Osaka University, Osaka 565-0871, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kunisawa
authors.affiliation: 1] Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan [2] Graduate School of Medical Life Science, Yokohama City University, Kanagawa 230-0045, Japan [3] Departments of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan [4] Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Tokyo 102-8666, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Arita
authors.affiliation: Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hayasaka
authors.affiliation: Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Harada
authors.affiliation: Departments of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Iwamoto
authors.affiliation: 1] Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan [2] Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Nagasawa
authors.affiliation: 1] Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan [2] Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Shikata
authors.affiliation: Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nagatake
authors.affiliation: Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: 1] Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan [2] Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Hashimoto
authors.affiliation: 1] Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan [2] Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kurashima
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: 1] Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo 102-0075, Japan [2] Departments of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.affiliation: 1] Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan [2] The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Setou
authors.affiliation: 1] Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan [2] International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan [3] Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo 102-0075, Japan [4] Department of Medical Genome Science, Graduate School of Frontier Science, The University of Tokyo, Chiba 277-8562, Japan [5] Department of Medical Genome Science, Graduate School of Frontier Science, The University of Tokyo, Chiba 277-8562, Japan [6] Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan [7] Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005512:Food Hypersensitivity / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D008043:Linseed Oil / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D015525:Fatty Acids, Omega-3; D008043:Linseed Oil