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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 CD69 hi CCR3 low CXCR4 - 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 (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.

Original languageEnglish
JournalAllergy: European Journal of Allergy and Clinical Immunology
DOIs
Publication statusPublished - 2019 Jan 1

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Nasal Polyps
Eosinophils
Fatty Acids
Arachidonate 15-Lipoxygenase
Lipid Metabolism
Proteomics
Healthy Volunteers
Sialic Acid Binding Immunoglobulin-like Lectins
Cytokines
Leukotriene D4
Pattern Recognition Receptors
Interleukin-5
Granulocyte-Macrophage Colony-Stimulating Factor
Chemokines
Granulocytes
Prostaglandins
Up-Regulation
Asthma
Phenotype
Lipids

Keywords

  • chronic rhinosinusitis
  • GGT5
  • human eosinophil
  • lipid mediator
  • multi-omics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Dysregulated fatty acid metabolism in nasal polyp-derived eosinophils from patients with chronic rhinosinusitis. / Miyata, Jun; Fukunaga, Koichi; Kawashima, Yusuke; Watanabe, Takashi; Saitoh, Akina; Hirosaki, Tomomi; Araki, Yasutomo; Kikawada, Toru; Betsuyaku, Tomoko; Ohara, Osamu; Arita, Makoto.

In: Allergy: European Journal of Allergy and Clinical Immunology, 01.01.2019.

Research output: Contribution to journalArticle

Miyata, Jun ; Fukunaga, Koichi ; Kawashima, Yusuke ; Watanabe, Takashi ; Saitoh, Akina ; Hirosaki, Tomomi ; Araki, Yasutomo ; Kikawada, Toru ; Betsuyaku, Tomoko ; Ohara, Osamu ; Arita, Makoto. / Dysregulated fatty acid metabolism in nasal polyp-derived eosinophils from patients with chronic rhinosinusitis. In: Allergy: European Journal of Allergy and Clinical Immunology. 2019.
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AU - Saitoh, Akina

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AB - 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 CD69 hi CCR3 low CXCR4 - 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 (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.

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