A novel role of-derived miR-276-3p in aggravating mite-induced allergic airway inflammation.

Abstract

(DFA), the most prevalent aeroallergen in allergic asthma, releases extracellular vesicles (EVs) containing dfa-miR-276-3p, which plays an important role in DFA sensitization. In this study, we utilized AAV-dfa-miR-276-3p to create a mouse model with dfa-miR-276-3p overexpression in lungs. Using this model, we demonstrated that dfa-miR-276-3p acted as a priming factor that exacerbated DFA extract (DFE)-induced airway inflammation in mice. We also confirmed that dfa-miR-276-3p functioned as a priming pro-inflammatory factor in human bronchial epithelial BEAS-2B cells, enhancing the release of inflammatory cytokines induced by DFE. Furthermore, we found that dfa-miR-276-3p regulated stanniocalcin 1 (STC1) in a targeted manner, leading to increased inflammatory cytokine secretion and activation of the reactive oxygen species (ROS)/nuclear factor kappa B (NF-κB) pathway. Notably, the addition of recombinant human STC1 alleviated the inflammatory effects of dfa-miR-276-3p, reducing airway inflammation and dampening ROS/NF-κB signaling. Parallel findings in mouse models confirmed that dfa-miR-276-3p drove DFA-induced airway inflammation through STC1-dependent regulation of the ROS/NF-κB pathway. Our study reveals a cross-kingdom regulatory role for DFA-derived miRNAs in the pathogenesis of allergic asthma, highlighting dfa-miR-276-3p as a crucial priming factor in the process of allergic airway inflammation induced by DFA.IMPORTANCEWe demonstrated that dfa-miR-276-3p acted as a priming factor that exacerbated(DFA) extract-induced airway inflammation in mice, and functioned as a priming pro-inflammatory factor in human bronchial epithelial BEAS-2B cells. In addition, dfa-miR-276-3p was found to regulate stanniocalcin 1 (STC1) in a targeted manner, leading to increased secretion of inflammatory cytokines and activation of the reactive oxygen species (ROS)/nuclear factor kappa B (NF-κB) pathway, and addition of recombinant human STC1 alleviated the inflammatory effects of dfa-miR-276-3p, reducing airway inflammation and dampening ROS/NF-κB signaling. Parallel findings in mouse models confirmed that dfa-miR-276-3p drove DFA-induced airway inflammation through STC1-dependent regulation of the ROS/NF-κB pathway. Our findings provide new insights into the role of DFA-derived miRNAs in the development of allergic asthma and propose an alternative pathway for DFA sensitization that may have significant clinical implications for allergy prevention and treatment.