2. Academic Validation
  3. House dust mite induced mucosal barrier dysfunction and type 2 inflammatory responses via the MAPK/AP-1/IL-24 Signaling pathway in allergic rhinitis

House dust mite induced mucosal barrier dysfunction and type 2 inflammatory responses via the MAPK/AP-1/IL-24 Signaling pathway in allergic rhinitis

  • Int Immunopharmacol. 2025 Feb 20:148:113972. doi: 10.1016/j.intimp.2024.113972.
Siyao Zhang 1,  Wanjuan Wu 1,  Min Gu 1,  Yun Zhao 2,  Lixin Wang 3,  Kai Liu 4,  Zhenkun Yu 5
Affiliations

Affiliations

  • 1 Department of Otolaryngology-Head and Neck Surgery, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, 71 Hexi Street, Nanjing 210019, Jiangsu, China; Nanjing Medical Key Laboratory of Laryngopharynx & Head and Neck Oncology, 71 Hexi Street, Nanjing 210019, Jiangsu, China.
  • 2 Department of General Surgery, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China.
  • 3 Department of Microbiology and Immunology, School of Medicine, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Southeast University, Nanjing 210009, China.
  • 4 Department of Otolaryngology-Head and Neck Surgery, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, 71 Hexi Street, Nanjing 210019, Jiangsu, China; Nanjing Medical Key Laboratory of Laryngopharynx & Head and Neck Oncology, 71 Hexi Street, Nanjing 210019, Jiangsu, China. Electronic address: assimy1986@126.com.
  • 5 Department of Otolaryngology-Head and Neck Surgery, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, 71 Hexi Street, Nanjing 210019, Jiangsu, China; Nanjing Medical Key Laboratory of Laryngopharynx & Head and Neck Oncology, 71 Hexi Street, Nanjing 210019, Jiangsu, China. Electronic address: yuzhenkun65@hotmail.com.
PMID: 39826453 DOI: 10.1016/j.intimp.2024.113972
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.

Keywords

AP-1; Allergic rhinitis; Epithelial barrier; IL-24; type 2 Inflammatory Responses.

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