PM2.5 exacerbates house dust mite-induced allergic rhinitis via STING-mediated nasal epithelial barrier disruption

Background The synergistic effect of PM2.5 and house dust mite (HDM) in exacerbating allergic rhinitis (AR) is recognized, but the underlying molecular mechanisms remain unclear. Objective This study investigated whether PM2.5 aggravates HDM-induced AR and nasal epithelial barrier damage via the STING signaling pathway. Methods This research combined bioinformatics analysis of a human nasal transcriptome dataset with in vivo (BALB/c mouse model) and in vitro (Human Nasal Epithelial Cells, HNEpCs) experiments. Models were exposed to PM2.5 and HDM, alone or in combination. Rhinitis symptoms, epithelial barrier integrity, Th2 inflammation, and the STING/NF-κB pathway were assessed. The STING inhibitor H-151 was used for functional validation. Results Bioinformatics analysis linked PM2.5 exposure to TNF/NF-κB signaling. In vivo and in vitro experiments consistently demonstrated that co-exposure to PM2.5 and HDM synergistically worsened nasal symptoms, Th2 responses (elevated IL-4, IL-5, IL-13, IgE), and impaired barrier function (downregulated E-cadherin and Claudin-1), while activating the STING/NF-κB pathway. Critically, H-151 treatment reversed these pathological changes. Conclusion PM2.5 disrupts the nasal epithelial barrier and synergizes with HDM to exacerbate allergic inflammation by activating the STING/NF-κB pathway. This study identifies STING as a potential therapeutic target for environment-aggravated allergic diseases.