Maternal ω3 docosapentaenoic acid inhibits infant allergic dermatitis through TRAIL-expressing plasmacytoid dendritic cells in mice

So ichiro Hirata, Takahiro Nagatake, Kento Sawane, Koji Hosomi, Tetsuya Honda, Sachiko Ono, Noriko Shibuya, Emiko Saito, Jun Adachi, Yuichi Abe, Junko Isoyama, Hidehiko Suzuki, Ayu Matsunaga, Takeshi Tomonaga, Hiroshi Kiyono, Kenji Kabashima, Makoto Arita, Jun Kunisawa

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Background: Maternal dietary exposures are considered to influence the development of infant allergies through changes in the composition of breast milk. Cohort studies have shown that ω3 polyunsaturated fatty acids (PUFAs) in breast milk may have a beneficial effect on the preventing of allergies in infants; however, the underlying mechanisms remain to be investigated. We investigated how the maternal intake of dietary ω3 PUFAs affects fatty acid profiles in the breast milk and their pups and reduced the incidence of allergic diseases in the pups. Methods: Contact hypersensitivity (CHS) induced by 2,4-dinitrofluorobenzene (DNFB) and fluorescein isothiocyanate was applied to the skin in pups reared by mother maintained with diets mainly containing ω3 or ω6 PUFAs. Skin inflammation, immune cell populations, and expression levels of immunomodulatory molecules in pups and/or human cell line were investigated by using flow cytometric, immunohistologic, and quantitative RT-PCR analyses. ω3 PUFA metabolites in breast milk and infant's serum were evaluated by lipidomics analysis using LC-MS/MS. Results: We show that maternal intake of linseed oil, containing abundant ω3 α-linolenic acid, resulted in the increased levels of ω3 docosapentaenoic acid (DPA) and its 14-lipoxygenation products in the breast milk of mouse dams; these metabolites increased the expression of TNF-related apoptosis-inducing ligand (TRAIL) on plasmacytoid dendritic cells (pDCs) in their pups and thus inhibited infant CHS. Indeed, the administration of DPA-derived 14-lipoxygenation products to mouse pups ameliorated their DNFB CHS. Conclusion: These findings suggest that an inhibitory mechanism in infant skin allergy is induced through maternal metabolism of dietary ω3 PUFAs in mice.

Original languageEnglish
Pages (from-to)1935-1951
Number of pages17
JournalAllergy: European Journal of Allergy and Clinical Immunology
Issue number8
Publication statusPublished - 2020 Aug 1


  • 14-lipoxygenation
  • breast milk
  • infant allergy
  • ω3 DPA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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