Dupilumab Alleviates IL-13-Induced Nasal Epithelial Barrier Dysfunction by Regulating Claudin-10 Expression.

Area of Science:

• Immunology
• Cell Biology
• Otorhinolaryngology

Background:

• Nasal epithelial barrier dysfunction is key in chronic rhinosinusitis with nasal polyps (CRSwNP).
• Mechanisms of tight junction (TJ) disruption in CRSwNP are not fully understood.
• The role of IL-13 in TJ breakdown and epithelial remodeling requires further investigation.

Purpose of the Study:

• To investigate the role of IL-13 in TJ disruption and epithelial remodeling in CRSwNP.
• To evaluate dupilumab's efficacy in restoring epithelial integrity under Type-2 inflammatory conditions.

Main Methods:

• Integrated transcriptomic data (GSE136825) with clinical samples to identify TJ-related genes.
• Utilized human nasal epithelial cells to assess the impact of IL-13 and dupilumab on barrier function (TER, CLDN10 expression) via RT-qPCR, Western blot, and immunofluorescence.
• Employed statistical analyses including ANOVA and correlation tests.

Main Results:

• Claudin-10 (CLDN10) was significantly downregulated in CRSwNP and correlated with reduced eosinophil infiltration.
• IL-13 exposure reduced CLDN10 expression and transepithelial electrical resistance (TER), inducing goblet cell hyperplasia and decreasing club and ciliated cells.
• Dupilumab treatment reversed IL-13-induced CLDN10 loss, restored barrier integrity, and normalized epithelial alarmins (IL-25, TSLP).

Conclusions:

• IL-13-induced Type-2 inflammation impairs nasal epithelial barrier integrity by downregulating CLDN10 and altering cell differentiation.
• Dupilumab effectively restores CLDN10 expression and barrier function in CRSwNP.
• CLDN10 is a critical mediator of barrier dysfunction and a potential therapeutic target for CRSwNP.