House dust mite induced mucosal barrier dysfunction and type 2 inflammatory responses via the MAPK/AP-1/IL-24 Signaling pathway in allergic rhinitis
Siyao Zhang, Wen‐Lan Wu, Min Gu, Yun Zhao, Lixin Wang, Kai Liu, Zhenkun Yu
Abstract
The epithelial barrier, previously regarded only as a physical defense, is now understood to play a vital role in immune responses and the regulation of inflammation. Allergic rhinitis (AR) is a prevalent chronic inflammatory condition of the nasal mucosa, with House Dust Mite (HDM) identified as a significant inhalant allergen that can impair this barrier. IL-24 has emerged as a key cytokine in allergic diseases, involved in maintaining epithelial cell homeostasis. Nevertheless, the underlying mechanisms of these effects remain inadequately understood. This study explores HDM-induced IL-24 secretion and mucosal barrier impairment using patient and animal tissue samples. Our results confirm that HDM sensitization triggers inflammatory changes in the nasal cavity, with IL-24 acting as a key mediator of type 2 inflammation and AR severity. HDM enhances IL-24 secretion via the P38 MAPK pathway and transcription factor AP-1, while IL-24 downregulates occludin and ZO-1 expression through the STAT1/STAT3 signaling pathway, compromising barrier function and increasing permeability. Furthermore, IL-24 promotes IL-33 secretion, further exacerbating the inflammatory response in AR. These findings clarify the mechanisms of epithelial barrier disruption in HDM-sensitized allergic rhinitis and suggest that modulating the IL-24 signaling pathway may serve as a promising therapeutic strategy to restore barrier integrity in AR.