Dysregulated fatty acid metabolism in nasal polyp-derived eosinophils from patients with chronic rhinosinusitis

Jun Miyata, Koichi Fukunaga, Yusuke Kawashima, Takashi Watanabe, Akina Saitoh, Tomomi Hirosaki, Yasutomo Araki, Toru Kikawada, Tomoko Betsuyaku, Osamu Ohara, Makoto Arita

研究成果: Article査読

53 被引用数 (Scopus)


Background: Eosinophils are multifunctional granulocytes capable of releasing various cytokines, chemokines, and lipid mediators. We previously reported dysregulated fatty acid metabolism in peripheral blood-derived eosinophils from patients with severe asthma. However, functional characteristics of eosinophils present in allergic inflammatory tissues remain largely uncharacterized. Methods: We established a method for isolating CD69hi CCR3low CXCR4- siglec-8int eosinophils from nasal polyps of patients with eosinophilic rhinosinusitis (NP-EOS). Multi-omics analysis including lipidomics, proteomics, and transcriptomics was performed to analyze NP-EOS as compared to peripheral blood-derived eosinophils from healthy subjects (PB-EOS). Results: Lipidomic analysis revealed impaired synthesis of prostaglandins and 15-lipoxygenase (15-LOX)-derived mediators, and selective upregulation of leukotriene D4 production. Furthermore, proteomics and transcriptomics revealed changes in the expression of specific enzymes (GGT5, DPEP2, and 15-LOX) responsible for dysregulated lipid metabolism. Ingenuity pathway analysis indicated the importance of type 2 cytokines and pattern recognition receptor pathways. Stimulation of PB-EOS with eosinophil activators IL-5, GM-CSF, and agonists of TLR2 and NOD2 mimicked the observed changes in lipid metabolism. Conclusion: Inflammatory tissue-derived eosinophils possess a specific phenotype with dysregulated fatty acid metabolism that may be targeted therapeutically to control eosinophilic inflammatory diseases.

ジャーナルAllergy: European Journal of Allergy and Clinical Immunology
出版ステータスPublished - 2019 6月

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学


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