Targeting Tight Junction Proteins to Restore Airway Epithelial Barrier Function in Asthma

Asthma is increasingly recognized not only as an inflammatory disorder but also as a disease rooted in airway epithelial barrier dysfunction. This review examines tight junction proteins (TJPs) including occludin, claudins, and ZO family members, as central regulators of epithelial integrity and potential therapeutic targets.

Disruption of TJPs is an early and pivotal event in asthma, enabling allergen penetration, amplifying immune responses, and promoting airway remodeling. Mechanistic studies reveal TJP regulation involves intricate crosstalk with inflammatory pathways, cytoskeletal remodeling, and epigenetic modulation. Emerging strategies including biologics, small molecules, and targeted delivery systems, demonstrate preclinical efficacy in restoring barrier function, though patient heterogeneity and delivery limitations remain challenges. Restoring epithelial barrier integrity through TJP modulation represents a paradigm shift from conventional anti-inflammatory therapy to precision, disease-modifying interventions. Biomarker-guided, targeted approaches offer the potential to interrupt the self-perpetuating cycle of epithelial damage and inflammation, positioning barrier repair as a central goal in next-generation asthma management.