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The following is a summary of “Extracellular vesicle miRNAs drive aberrant macrophage responses in NSAID-exacerbated respiratory disease,” published in the April 2024 issue of Allergy & Immunology by Hartung, et al.

Extracellular vesicles (EVs) have been suggested to play a role in the development of asthma, yet their specific contributions to immune dysfunction and type 2 airway inflammation remain not fully understood. For a study, researchers sought to explore the roles of airway EVs and their miRNA cargo in the pathogenesis of NSAID-exacerbated respiratory disease (N-ERD), a severe form of type 2 inflammation in the airways.

The study isolated EVs from induced sputum and supernatants of cultured nasal polyp or turbinate tissues from patients with both N-ERD and healthy controls using size-exclusion chromatography. The isolated EVs were characterized through particle tracking, electron microscopy, and miRNA sequencing. To assess the functional effects of EV miRNAs, experiments were conducted using human macrophages and normal human bronchial epithelial cells (NHBEs). These experiments involved RNA sequencing, LC-MS/MS for protein analysis, and multiplex cytokine assays.

The study found that EVs were highly prevalent in patients with N-ERD upper and lower airway secretions. Compared to EVs from healthy individuals, patients with N-ERD exhibited significant alterations in both immunostimulatory capacity and miRNA profiles. Specifically, N-ERD airway EVs, but not those from healthy controls, triggered the production of inflammatory cytokines GM-CSF and IL-8 in NHBEs. In macrophages, N-ERD airway EVs showed a reduced ability to stimulate cytokine and prostanoid production while promoting M2 macrophage activation. Notably, the let-7 family of miRNAs was found to be highly enriched in the sputum EVs of patients with N-ERD and was shown to replicate the suppressive effects of N-ERD EVs on macrophage activation.

The study suggested that aberrant miRNA profiles in airway EVs may play a significant role in immune dysfunction and sustained type 2 inflammation in N-ERD. Specifically, let-7 family miRNAs were identified as potential therapeutic targets for addressing defective macrophage activation and mediator responses in N-ERD.

Reference: onlinelibrary.wiley.com/doi/10.1111/all.16117