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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

Corresponding Author:[email protected]

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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.
25 Sep 2020Published in Frontiers in Cell and Developmental Biology volume 8. 10.3389/fcell.2020.572749