Extracellular vesicle miRNAs drive aberrant macrophage responses in NSAID-exacerbated respiratory disease.

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State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_2572ABA6A7A8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Extracellular vesicle miRNAs drive aberrant macrophage responses in NSAID-exacerbated respiratory disease.
Journal
Allergy
Author(s)
Hartung F., Haimerl P., Schindela S., Mussack V., Kirchner B., Henkel FDR, Bernhardt U., Zissler U.M., Santarella-Mellwig R., Pfaffl M., Schmidt-Weber C.B., Chaker A.M., Esser-von Bieren J.
ISSN
1398-9995 (Electronic)
ISSN-L
0105-4538
Publication state
Published
Issued date
07/2024
Peer-reviewed
Oui
Volume
79
Number
7
Pages
1893-1907
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Extracellular vesicles (EVs) have been implicated in the pathogenesis of asthma, however, how EVs contribute to immune dysfunction and type 2 airway inflammation remains incompletely understood. We aimed to elucidate roles of airway EVs and their miRNA cargo in the pathogenesis of NSAID-exacerbated respiratory disease (N-ERD), a severe type 2 inflammatory condition.
EVs were isolated from induced sputum or supernatants of cultured nasal polyp or turbinate tissues of N-ERD patients or healthy controls by size-exclusion chromatography and characterized by particle tracking, electron microscopy and miRNA sequencing. Functional effects of EV miRNAs on gene expression and mediator release by human macrophages or normal human bronchial epithelial cells (NHBEs) were studied by RNA sequencing, LC-MS/MS and multiplex cytokine assays.
EVs were highly abundant in secretions from the upper and lower airways of N-ERD patients. N-ERD airway EVs displayed profoundly altered immunostimulatory capacities and miRNA profiles compared to airway EVs of healthy individuals. Airway EVs of N-ERD patients, but not of healthy individuals induced inflammatory cytokine (GM-CSF and IL-8) production by NHBEs. In macrophages, N-ERD airway EVs exhibited an impaired potential to induce cytokine and prostanoid production, while enhancing M2 macrophage activation. Let-7 family miRNAs were highly enriched in sputum EVs from N-ERD patients and mimicked suppressive effects of N-ERD EVs on macrophage activation.
Aberrant airway EV miRNA profiles may contribute to immune dysfunction and chronic type 2 inflammation in N-ERD. Let-7 family miRNAs represent targets for correcting aberrant macrophage activation and mediator responses in N-ERD.
Keywords
Humans, Extracellular Vesicles/metabolism, Extracellular Vesicles/immunology, MicroRNAs/genetics, Macrophages/immunology, Macrophages/metabolism, Anti-Inflammatory Agents, Non-Steroidal/adverse effects, Cytokines/metabolism, Male, Female, Middle Aged, Macrophage Activation/immunology, Macrophage Activation/genetics, Adult, CRSwNP, asthma, extracellular vesicles, macrophages, type 2 immunity
Pubmed
Web of science
Open Access
Yes
Create date
08/04/2024 13:16
Last modification date
13/07/2024 6:12
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