Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Oct 22.
doi: 10.1111/all.70115. Online ahead of print.

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

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

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

Zhi-Qun Huang et al. Allergy. .

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.

PubMed Disclaimer

References

    1. A. Kato, A. T. Peters, W. W. Stevens, R. P. Schleimer, B. K. Tan, and R. C. Kern, “Endotypes of Chronic Rhinosinusitis: Relationships to Disease Phenotypes, Pathogenesis, Clinical Findings, and Treatment Approaches,” Allergy 77, no. 3 (2022): 812–826, https://doi.org/10.1111/all.15074.
    1. W. J. Fokkens, V. J. Lund, C. Hopkins, et al., “European Position Paper on Rhinosinusitis and Nasal Polyps 2020,” Rhinology 58, no. Suppl S29 (2020): 1–464, https://doi.org/10.4193/Rhin20.600.
    1. T. Delemarre, G. Holtappels, N. De Ruyck, et al., “A Substantial Neutrophilic Inflammation as Regular Part of Severe Type 2 Chronic Rhinosinusitis With Nasal Polyps,” Journal of Allergy and Clinical Immunology 147, no. 1 (2021): 179–188, https://doi.org/10.1016/j.jaci.2020.08.036.
    1. B. Liao, J. X. Liu, Z. Y. Li, et al., “Multidimensional Endotypes of Chronic Rhinosinusitis and Their Association With Treatment Outcomes,” Allergy 73, no. 7 (2018): 1459–1469, https://doi.org/10.1111/all.13411.
    1. U. C. Kucuksezer, C. Ozdemir, M. Akdis, and C. A. Akdis, “Chronic Rhinosinusitis: Pathogenesis, Therapy Options, and More,” Expert Opinion on Pharmacotherapy 19, no. 16 (2018): 1805–1815, https://doi.org/10.1080/14656566.2018.1527904.

LinkOut - more resources