日本香粧品学会誌〈講Vol. 45, No. 4, pp. 348–352（2021）

演〉

第 46 回日本香粧品学会（2021）・特別講演 I

皮膚に及ぼす食の免疫学的影響の理解と応用
長 竹 貴 広 1，國 澤純 1–5 , *Diet-Mediated Immune Regulation in the Skin
Takahiro NAGATAKE1, Jun KUNISAWA1–5, *Abstract
Immune system is regulated by not only genetic background but also environmental factors including diets. Accumulating evidence indicates that ω3 fatty acids exert anti-inﬂammatory properties and recent advances in the metabolome analysis
revealed that fatty acid metabolism plays a key role in the regulation of skin allergic inﬂammation. We found that fatty acidmetabolism varies among tissues. For example, 17,18-epoxyeicosatetraenoic acid (17,18-EpETE) and 12-hydroxyeicosapentaenoic acid (12-HEPE) were generated from eicosapentaenoic acid in the gut and skin, respectively when mice were maintained on a diet containing linseed oil which is high in ω3 α-linolenic acid. In addition, both 17,18-EpETE and 12-HEPE
ameliorated contact hypersensitivity by inhibiting neutrophil inﬁltration through diﬀerent mechanisms. 17,18-EpETE acted
directly on neutrophils to block pseudopod formation in a GPR40-dependent manner, while 12-HEPE acted on keratinocytes
to suppress chemokine production for neutrophil recruitment in an RXRα-dependent manner. We further found that maternal intake of linseed oil ameliorated skin allergic inﬂammation in their pups, which was mediated by breast milk containing
14-hydroxydocosapentaenoic acid (14-HDPA). In pups, 14-HDPA induced the expression of TNF super family, TRAIL, on
plasmacytoid dendritic cells and consequently inhibited inﬂammatory cytokine production from T cells. As another example,
when mice were maintained on a diet containing coconut oil which has little amounts of essential fatty acids, mead acid was
uniquely produced from oleic acid, which in turn ameliorated contact hypersensitivity through the inhibition of neutrophil
pseudopod formation, leukotriene B4 production and increment of vascular permeability. These results demonstrate that thefatty acid composition and metabolism are a critical determinant of beneﬁcial eﬀects of dietary lipids on the control of skinallergic inﬂammation.
Key words: dietary lipids, essential fatty acids, metabolism, dermatitis, allergy.

1.

られているが，食に秘められた生体調節機能は栄養機はじめに能，嗜好機能とともに食品の三大機能の 1 つとして認知

17 世 紀 の イ ギ リ ス 詩 人 ジ ョ ー ジ・ ハ ー バ ー ト はされ，多くの研究報告の蓄積と共に，近年では食の効果「Whatsoever was the father of a disease, an ill diet was theを，化合物と生体分子との反応として分子レベルで科学mother（ 病気の原因の「父」に当たるものが何であれ，的に語ることができるようになってきた。

「母」に当たるものは「間違った食事」である）」と述べ

食品由来のさまざまな成分が生体調節作用を有するこている。日本でも古来より「医食同源」という概念が知とが知られているが，脂質（油）も重要な分子として注目

国立研究開発法人医薬基盤・健康・栄養研究所ワクチン・ア
ジュバント研究センターワクチンマテリアルプロジェクト／
腸内環境システムプロジェクト
2
大阪大学大学院医学系研究科／薬学研究科／歯学研究科／理学研究科
3
神戸大学大学院医学研究科
4
東京大学医科学研究所国際粘膜ワクチン開発研究センター
5
早稲田大学ナノ・ライフ創新研究機構
1

1

Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant
Research and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition (7–6–8 Asagi
Saito, Ibaraki, Osaka 567–0085, Japan)
2
Graduate School of Medicine/Graduate School of PharmaceuticalSciences/Graduate School of Dentistry/Graduate School of Science,
Osaka University
3
Graduate School of Medicine, Kobe University
4
International Research and Development Center for Mucosal Vac* Corresponding author：国立研究開発法人医薬基盤・健康・栄養 cines, the Institute of Medical Science, The University of Tokyo研究所ワクチン・アジュバント研究センターワクチンマテリ 5 Research Organization for Nano & Life Innovation, Waseda Univerアルプロジェクト／腸内環境システムプロジェクト，〒567–sity0085 大 阪 府 茨 木 市 彩 都 あ さ ぎ 7–6–8（E-mail: kunisawa@nibiohn.go.jp）