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Interleukin-13 alters tight junction proteins expression thereby compromising barrier function and dampens rhinovirus induced immune responses in nasal epithelium
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  • Zhi-Qun Huang,
  • Jing Liu,
  • Hsiao Hui Ong,
  • Tian Yuan,
  • Xiang-Min Zhou,
  • Jun Wang,
  • Tan Kai-Sen,
  • Vincent Chow,
  • Qin-Tai Yang,
  • Li Shi,
  • Jing Ye,
  • De Yun Wang
Zhi-Qun Huang
First Affiliated Hospital of Nanchang University
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Jing Liu
National University of Singapore - Kent Ridge Campus
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Hsiao Hui Ong
National University Singapore Yong Loo Lin School of Medicine
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Tian Yuan
The Third Affiliated Hospital Sun Yat-sen University
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Xiang-Min Zhou
Second Hospital of Shandong University
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Jun Wang
First Affiliated Hospital of Nanchang University
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Tan Kai-Sen
National University of Singapore
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Vincent Chow
National University Singapore Yong Loo Lin School of Medicine
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Qin-Tai Yang
The Third Affiliated Hospital, Sun Yat-sen University
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Li Shi
Second Hospital of Shandong University
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Jing Ye
First Affiliated Hospital of Nanchang University
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De Yun Wang
Yong Loo Lin School of Medicine, National University of Singapore
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Abstract

Background: Tight junctions (TJs) are intracellular structures which are essential for epithelial barrier function and play an important role in antimicrobial defense. Epithelium dysfunction and type-2-skewed inflammation are two main pathological phenomena of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the effect of pro-inflammatory type-2 cytokine interleukin-13 (IL-13) on TJs in CRSwNP is poorly understood. Methods: Nasal biopsies of 70 CRSwNP patients and 25 healthy subjects, and in vitro IL-13-matured human nasal epithelial cells (hNECs) in 9 persons were used to analyze epithelial markers and TJ proteins. Epithelium permeability, transepithelial electrical resistance (TEER), mRNA and protein expression of TJs were quantified for IL-13-matured hNECs and that with RV infection. Results: Both mRNA and protein expression of occludin, claudin-3 and ZO-1 were significantly decreased in CRSwNP biopsies and in hNECs after IL-13 treatment. Differentiation of hNECs with IL-13 treatment increased epithelium permeability, decreased TEER and altered hNECs composition resulting in lesser ciliated cells and mucus over-secretion. Interestingly, claudin-3 is selectively expressed on ciliated cells. While RV infection induced minimal changes to TJs, the IL-13-matured hNECs has reduced capacity for upregulation of IFN-λ1 and CXCL10 but further increased the expression of TSLP upon acute RV infection. Conclusions: These findings suggested that IL-13-mediated dysfunction of TJs and compromised epithelial barrier. IL-13-induced cilia loss conferred lowered viral replication and impaired antiviral responses of nasal epithelium against acute RV infection.