1. Dysregulated fatty acid metabolism in nasal polyp-derived eosinophils from patients with chronic rhinosinusitis
- Author
-
Tomoko Betsuyaku, Yusuke Kawashima, Osamu Ohara, Makoto Arita, Jun Miyata, Koichi Fukunaga, Akina Saitoh, Yasutomo Araki, Toru Kikawada, Tomomi Hirosaki, and Takashi Watanabe
- Subjects
Adult ,Male ,Chemokine ,Proteome ,Immunology ,Blood Donors ,Leukotriene D4 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Nasal Polyps ,NOD2 ,medicine ,Immunology and Allergy ,Arachidonate 15-Lipoxygenase ,Humans ,Nasal polyps ,Sinusitis ,Cells, Cultured ,Rhinitis ,biology ,Fatty acid metabolism ,business.industry ,Fatty Acids ,Pattern recognition receptor ,Lipid metabolism ,Lipid signaling ,gamma-Glutamyltransferase ,respiratory system ,Eosinophil ,Middle Aged ,medicine.disease ,Eosinophils ,medicine.anatomical_structure ,Phenotype ,030228 respiratory system ,chemistry ,Prostaglandin-Endoperoxide Synthases ,Chronic Disease ,biology.protein ,Cytokines ,Female ,business ,Transcriptome ,030215 immunology ,Signal Transduction - Abstract
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.
- Published
- 2018