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Dysregulated fatty acid metabolism in nasal polyp‐derived eosinophils from patients with chronic rhinosinusitis
Author(s) -
Miyata Jun,
Fukunaga Koichi,
Kawashima Yusuke,
Watanabe Takashi,
Saitoh Akina,
Hirosaki Tomomi,
Araki Yasutomo,
Kikawada Toru,
Betsuyaku Tomoko,
Ohara Osamu,
Arita Makoto
Publication year - 2019
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13726
Subject(s) - lipid metabolism , eosinophil , leukotriene , immunology , nasal polyps , chemokine , fatty acid metabolism , lipid signaling , biology , medicine , inflammation , fatty acid , biochemistry , asthma
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 CD 69 hi CCR 3 low CXCR 4 ‐ siglec‐8 int 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 D 4 production. Furthermore, proteomics and transcriptomics revealed changes in the expression of specific enzymes ( GGT 5, DPEP 2, 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 TLR 2 and NOD 2 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.