Quantitative Analysis Reveals IL-17A Widens Nasal Epithelial Tight Junction Gaps via AMPK in Allergic Rhinitis.

BACKGROUND

Allergic rhinitis (AR) is a chronic IgE-mediated inflammatory disease characterized by nasal epithelial barrier dysfunction. Interleukin-17A (IL-17A) has been implicated in epithelial barrier disruption, but its role in regulating nasal epithelial tight junctions (TJs) remains unclear.

OBJECTIVE

To investigate the effects of IL-17A on nasal epithelial TJs integrity and determine whether adenosine monophosphate-activated protein kinase (AMPK) signaling mediates IL-17A-induced barrier dysfunction in AR.

METHODS

Inferior turbinate tissues from patients with AR and healthy controls were analyzed by transmission electron microscopy, quantitative PCR, western blotting, and immunofluorescence. Human nasal epithelial cells cultured at an air-liquid interface were stimulated with IL-17A for 28 days. TJs integrity was assessed by transepithelial electrical resistance, fluorescein isothiocyanate-dextran permeability, and automated ImageJ-based quantification of TJs morphology. Bulk RNA sequencing was performed, and AMPK activity was modulated using AICAR and Compound C.

RESULTS

AR tissues exhibited disrupted TJs and suppressed AMPK activity. IL-17A expression was elevated and negatively correlated with TJs protein levels. In human nasal epithelial cells, IL-17A reduced TJs protein expression, decreased transepithelial electrical resistance, increased paracellular permeability, and widened intercellular spaces. Transcriptomic analysis demonstrated suppression of AMPK signaling after IL-17A stimulation. Activation of AMPK with AICAR restored TJs expression and improved barrier function.

CONCLUSION

IL-17A impairs nasal epithelial barrier integrity by inhibiting AMPK signaling, whereas AMPK activation rescues TJs structure and function, identifying the IL-17A/AMPK axis as a potential therapeutic target in allergic rhinitis.