Plasma extracellular vesicles regulate the Functions of Th2 and ILC2 cells via miRNA-150-5p in patients with allergic rhinitis

Abstract

Allergic rhinitis (AR), a chronic airway inflammation, has witnessed a rising prevalence in recent decades. Recent research indicates that various EVs are released into plasma in allergic airway inflammation, correlating with impaired airway function and severe inflammation. However, the contribution of plasma EVs to AR pathogenesis remains incompletely understood. We isolated plasma EVs using differential ultracentrifugation or size exclusion chromatography (SEC) and obtained differential microRNA (miRNA) expression profiles through miRNA sequencing. Peripheral blood mononuclear cells (PBMCs) were exposed to plasma EVs and miRNA mimics and inhibitors to assess the effect of plasma EVs and the underlying mechanisms. We found that EVs from HC and AR patients exhibited comparable characteristics in terms of concentration, structure, and EV marker expression. AR-EVs significantly enhanced Th2 cell levels and promoted ILC2 differentiation and IL-13⁺ ILC2 levels compared to HC-EVs. Both HC-EVs and AR-EVs were efficiently internalized by CD4⁺ T cells and ILCs. miRNA sequencing of AR-EVs revealed unique miRNA signatures implicated in diverse biological processes, among which miR-150-5p, miR-144-3p, miR-10a-5p, and miR-10b-5p were identified as pivotal contributors to AR-EVs’ effects on CD4⁺ T cells and ILC2s. MiR-150-5p exhibited the most pronounced impact on cell differentiation and was confirmed to be upregulated in AR-EVs by PCR. In total, our study demonstrated that plasma EVs from patients with AR exhibited a pronounced capacity to significantly enhance the differentiation of Th2 cells and ILC2, which was correlated with an elevated expression of miR-150-5p within AR-EVs. These findings contribute to the advancement of our comprehension of EVs in the pathogenesis of AR and hold the potential to unveil novel therapeutic targets for the treatment of AR.