Tight junctions (TJs) are intercellular 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 IL-13 on TJs in CRSwNP is poorly understood. Nasal biopsies of CRSwNP patients and in vitro IL-13-matured human nasal epithelial cells (hNECs) were used to analyze epithelial markers and TJ proteins. Epithelium permeability, transepithelial electrical resistance (TEER), expression of TJs were quantified for IL-13-matured hNECs and that with RV infection. The expression of occludin, claudin-3, and ZO-1 were significantly decreased in CRSwNP biopsies and in hNECs after IL-13 treatment. 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 RV infection. 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 RV infection.

紧密连接（TJ）是细胞间结构，对上皮屏障功能至关重要，并且在抗菌防御中起重要作用。上皮功能障碍和2型偏斜炎症是慢性鼻鼻窦炎伴鼻息肉（CRSwNP）的两种主要病理现象。然而，促炎的2型细胞因子IL-13对CRSwNP中TJ的作用了解甚少。CRSwNP患者的鼻活检和体外IL-13成熟的人鼻上皮细胞（hNECs）用于分析上皮标志物和TJ蛋白。定量分析IL-13成熟的hNEC和RV感染的上皮渗透性，跨上皮电阻（TEER），TJ的表达。IL-13治疗后，CRSwNP活检和hNEC中occludin，claudin-3和ZO-1的表达明显降低。IL-13处理可增加上皮通透性，降低TEER并改变hNECs组成，从而减少纤毛细胞和粘液过度分泌。有趣的是，claudin-3在纤毛细胞上选择性表达。尽管RV感染对TJ的影响微乎其微，但IL-13成熟的hNEC却降低了TJ的上调能力。干扰素λ1个 和 CXCL10 但进一步增加了 TSLP在RV感染后。这些发现提示IL-13介导的TJ功能障碍和上皮屏障受损。IL-13引起的纤毛损失赋予病毒复制减少和鼻上皮抗RV感染的抗病毒反应受损。