Respiratory Syncytial Virus Infection Disrupts Airway Epithelial Barriers via IL‐33/ST2/MyD88 Signaling Axis

mice compared with wild-type controls. In vitro, the RSV-induced epithelial barrier disruption was exacerbated by topical application of exogenous IL-33, partially through activation of MyD88-mediated NF-κB signaling. Notably, knockdown of St2 by siRNA transfection or pharmacological inhibition of MyD88 partially restored the expression of E-cadherin, ZO-1 and Occludin in RSV-infected epithelial cells. RSV infection triggers robust IL-33 release from airway epithelial cells, leading to disrupted expression of AJC protein via activation of the MyD88-dependent NF-κB signaling pathway. These findings highlight the IL-33/ST2/MyD88 axis as a critical mediator of epithelial barrier dysfunction, which may represent a potential target for therapeutic intervention in RSV-mediated lung diseases.