2. Academic Validation
  3. Club Cells in Nasal Epithelial Repair: Insights From an IL-13-Induced Inflammatory Model

Club Cells in Nasal Epithelial Repair: Insights From an IL-13-Induced Inflammatory Model

  • Allergy. 2025 Oct 22. doi: 10.1111/all.70115.
Zhi-Qun Huang 1 2 3,  Jing Liu 2,  Jing Ye 3,  Li-Ying Sun 4,  Hsiao Hui Ong 2,  Yang Peng 5,  Bing-Qi Lin 5,  Jun-Hao Tu 2,  Ke-Shuang Wang 2,  Yi-Shan Xiong 3,  Qing Luo 3,  Mark Thong 6,  Yu Xu 1,  De-Yun Wang 2
Affiliations

Affiliations

  • 1 Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
  • 2 Department of Otolaryngology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • 3 Department of Allergy, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, China.
  • 4 First School of Clinical Medicine, Renmin Hospital of Wuhan University, Wuhan, China.
  • 5 State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China.
  • 6 Department of Otolaryngology, Head and Neck Surgery, National University Hospital, National University Health System, Singapore, Singapore.
PMID: 41123053 DOI: 10.1111/all.70115
Abstract

Background: Club cells, originating from basal cells, can differentiate into ciliated or goblet cells in the lower respiratory tract, but their role in nasal epithelium during chronic rhinosinusitis with nasal polyps (CRSwNP) is not well understood. We aim to investigate the role of club cells in CRSwNP and their biological mechanism in an IL-13-induced inflammation model of human nasal epithelial cells (HNECs).

Methods: CRSwNP was classified into four endotypes (N-E-, N+E-, N-E+, and N+E+) based on neutrophil and eosinophil infiltration. The expression of basal (TP63+), club (SCGB1A1+), ciliated (βIV-tubulin+), and goblet cells (MUC5AC+) was assessed in healthy controls (n = 23) and CRSwNP (n = 73) using RT-qPCR, western blot (WB), and immunofluorescence. The effects of IL-13, Dupilumab, and STAT6 Inhibitor (AS1517499) on cell differentiation were investigated in HNECs (n = 9) through RT-qPCR, WB, and flow cytometry (FCM).

Results: Club and ciliated cells significantly decreased in four endotypes of CRSwNP (all p < 0.001), while basal and goblet cells increased in neutrophilic and eosinophilic CRSwNP, respectively (all p < 0.05). In vitro, IL-13-induced significant cilia loss and MUC5AC secretion compared to IFN-γ and IL-17A (all p < 0.05), and FCM revealed a shift from SCGB1A1+βIV-tubulin+ to SCGB1A1+MUC5AC+ cells by IL-13-treated (all p < 0.05). Furthermore, Dupilumab mitigated IL-13-induced changes more effectively than AS1517499 (all p < 0.05).

Conclusions: Club cells are crucial in nasal epithelial repair, which is notably compromised in CRSwNP. This impairment is highlighted in an IL-13-induced inflammation model of nasal epithelium and further underscored by the therapeutic effect of Dupilumab in restoring epithelial repair mechanisms.

Keywords

IL‐13; chronic rhinosinusitis with nasal polyps; club cells; dupilumab; nasal epithelial repair.

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