HMGB1 impairs nasal mucosa epithelial barrier function in allergic rhinitis by promoting BECN1-mediating autophagy.

As a potent proinflammatory cytokine, high mobility group box 1 (HMGB1) exacerbates nasal mucosal epithelial barrier dysfunction. This study elucidates the mechanistic role of HMGB1 in driving epithelial barrier impairment in allergic rhinitis (AR). HMGB1 knockdown in human nasal epithelial cells (hNEpiC) significantly reduced LC3B expression and other autophagy markers, indicating suppressed autophagic activity. Notably, HMGB1 deficiency conferred resistance to IL-4-induced barrier dysfunction, manifested by increased transepithelial electrical resistance (TEER), decreased FITC-dextran permeability, and upregulated tight junction protein expressions (ZO-1, Occludin, and Claudin-1). Mechanistically, luciferase reporter assays demonstrated HMGB1's capacity to activate the BECN1 promoter, establishing a transcriptional regulatory mechanism. Crucially, BECN1 silencing abolished both HMGB1-induced autophagy and subsequent epithelial barrier disruption. Our findings identify HMGB1 as a critical mediator of AR progression through BECN1-dependent autophagy activation, suggesting that targeting this axis may represent a novel therapeutic strategy for AR management.