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.

Sharing Experience in the Application ofDistributed Map of Intractable Epistaxis in Concealed SitesHuiyi. Deng1, #, Huijun. Qiu1, #, Weihao Wang1, Qintai. Yang1,2, *1 Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China2 Department of Allergy, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China# The authors contributed equally to this work.* Corresponding authorQintai Yang, MD, PhDDepartment of Otolaryngology-Head and Neck SurgeryDepartment of AllergyThe Third Affiliated Hospital, Sun Yat-sen UniversityNo. 600 Tianhe Road, Guangzhou 510630, ChinaPhone: 020-85252239E-mail: [email protected]