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Release date：2019-02-20

Allergy：
[IF:6.048]
Dysregulated fatty acid metabolism in nasal polyp-derived eosinophils from patients with chronic rhinosinusitis
DOI: 10.1111/all.13726
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 remains 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 with 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.
First Author:
Jun Miyata
Corresponding authorLaboratory for Metabolomics RIKEN Center for Integrative Medical Sciences 1-7-22 Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
All Authors:
Jun Miyata, Koichi Fukunaga, Yusuke Kawashima, Takashi Watanabe, Akina Saitoh,Tomomi Hirosaki, Yasutomo Araki, Toru Kikawada, Tomoko Betsuyaku, Osamu Ohara,Makoto Arita

2019-01-25 Article