Inflammatory profile of eosinophils in asthma-COPD overlap and eosinophilic COPD: a multi-omics study.

Autor:	Sunata K; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.; Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan., Miyata J; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.; Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan., Kawashima Y; Department of Applied Genomics, Kazusa DNA Research Institute, Chiba, Japan., Konno R; Department of Applied Genomics, Kazusa DNA Research Institute, Chiba, Japan., Ishikawa M; Department of Applied Genomics, Kazusa DNA Research Institute, Chiba, Japan., Hasegawa Y; Department of Applied Genomics, Kazusa DNA Research Institute, Chiba, Japan., Onozato R; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan., Otsu Y; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan., Matsuyama E; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan., Sasaki H; Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, Saitama, Japan., Okuzumi S; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan., Mochimaru T; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.; Department of Respiratory Medicine, National Hospital Organization Tokyo Medical Center, Tokyo, Japan., Masaki K; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan., Kabata H; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan., Chubachi S; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan., Arita M; Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.; Graduate School of Medical Life Science, Yokohama City University, Kanagawa, Japan.; Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, Japan.; Human Biology-Microbiome-Quantum Research Center (WPI-Bio2Q), Keio University, Tokyo, Japan., Fukunaga K; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Oct 08; Vol. 15, pp. 1445769. Date of Electronic Publication: 2024 Oct 08 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1445769
Abstrakt:	Introduction: Elevated blood eosinophil levels in patients with chronic obstructive pulmonary disease (COPD) with or without asthma are linked to increased exacerbations and the effectiveness of inhaled corticosteroid treatment. This study aimed to delineate the inflammatory cellular properties of eosinophils in patients with asthma-COPD overlap (ACO) and eosinophilic COPD (eCOPD). Methods: Eosinophils were isolated from the peripheral blood of healthy volunteers, patients with non-eCOPD, and those with ACO/eCOPD. Multi-omics analysis involving transcriptomics, proteomics, and lipidomics was performed, followed by bioinformatic data analyses. In vitro experiments using eosinophils from healthy volunteers were conducted to investigate the molecular mechanisms underlying cellular alterations in eosinophils. Results: Proteomics and transcriptomics analyses revealed cellular characteristics in overall COPD patients represented by viral infection (elevated expression of sterol regulatory element-binding protein-1) and inflammatory responses (elevated levels of IL1 receptor-like 1, Fc epsilon receptor Ig, and transmembrane protein 176B). Cholesterol metabolism enzymes were identified as ACO/eCOPD-related factors. Gene Ontology and pathway enrichment analyses demonstrated the key roles of antiviral responses, cholesterol metabolism, and inflammatory molecules-related signaling pathways in ACO/eCOPD. Lipidomics showed the impaired synthesis of cyclooxygenase-derived mediators including prostaglandin E2 (PGE2) in ACO/eCOPD. In vitro assessment confirmed that IL-33 or TNF-α stimulation combined with IL-5 and IFN-γ stimulation induced cellular signatures in eosinophils in ACO/eCOPD. Atorvastatin, dexamethasone, and PGE2 differentially modulated these inflammatory changes. Discussion: ACO/eCOPD is associated with viral infection and an inflammatory milieu. Therapeutic strategies using statins and inhaled corticosteroids are recommended to control these pathogenic changes. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Sunata, Miyata, Kawashima, Konno, Ishikawa, Hasegawa, Onozato, Otsu, Matsuyama, Sasaki, Okuzumi, Mochimaru, Masaki, Kabata, Chubachi, Arita and Fukunaga.)
Databáze:	MEDLINE
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