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

Area of Science:

• Environmental Health
• Immunology
• Molecular Biology

Background:

• The combined impact of PM2.5 and house dust mite (HDM) on allergic rhinitis (AR) is known, but molecular mechanisms are unclear.
• PM2.5 is a common air pollutant, and HDM is a major indoor allergen.
• Understanding their interaction is crucial for managing AR.

Purpose of the Study:

• To investigate if PM2.5 exacerbates HDM-induced AR and nasal epithelial barrier damage.
• To determine the role of the STING signaling pathway in this process.
• To identify potential therapeutic targets for environmentally aggravated allergic diseases.

Main Methods:

• Bioinformatics analysis of human nasal transcriptome data.
• In vivo studies using a BALB/c mouse model.
• In vitro experiments with Human Nasal Epithelial Cells (HNEpCs) exposed to PM2.5 and HDM, alone and combined.
• Assessment of rhinitis symptoms, epithelial barrier integrity, Th2 inflammation, and the STING/NF-κB pathway.
• Functional validation using a STING inhibitor (H-151).

Main Results:

• PM2.5 exposure was linked to TNF/NF-κB signaling via bioinformatics.
• Co-exposure to PM2.5 and HDM synergistically worsened nasal symptoms and Th2 responses (increased IL-4, IL-5, IL-13, IgE).
• Epithelial barrier function was impaired (decreased E-cadherin, Claudin-1), and the STING/NF-κB pathway was activated.
• STING inhibitor H-151 reversed these pathological changes.

Conclusions:

• PM2.5 disrupts the nasal epithelial barrier and exacerbates HDM-induced allergic inflammation.
• Activation of the STING/NF-κB pathway is a key mechanism in this synergistic effect.
• STING represents a potential therapeutic target for allergic diseases aggravated by environmental factors.