2019年6月
Dysregulated fatty acid metabolism in nasal polyp-derived eosinophils from patients with chronic rhinosinusitis
Allergy: European Journal of Allergy and Clinical Immunology
- 巻
- 74
- 号
- 6
- 開始ページ
- 1113
- 終了ページ
- 1124
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1111/all.13726
- 出版者・発行元
- Allergy: European Journal of Allergy and Clinical Immunology
© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd. 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.
- リンク情報
-
- DOI
- https://doi.org/10.1111/all.13726
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/30667533
- 共同研究・競争的資金等の研究課題
- 「リポクオリティ」領域研究の推進
- 共同研究・競争的資金等の研究課題
- 脂肪酸クオリティの最先端リピドミクスと生理的意義の解明
- URL
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85062349732&origin=inward
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85062349732&origin=inward
- ID情報
-
- DOI : 10.1111/all.13726
- ISSN : 0105-4538
- eISSN : 1398-9995
- PubMed ID : 30667533
- SCOPUS ID : 85062349732