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

Abstract

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(BALB/c mouse model) and(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.andexperiments 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.