Interaction Of Thymic Stromal Lymphopoietin, IL-33,and Their Receptors In Epithelial Cells In Eosinophilic Chronic Rhinosinusitis With Nasal Polyps

Background:Although thymic stromal lymphopoietin (TSLP), IL-25, and1L-33system contribute to the initiation and development of Th2responses, their role in shaping distinct T helper (Th) responses in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) and their cross-regulation remain unclear. This study aimed to explore the involvement of TSLP, IL-25, IL-33, and their receptors in CRSwNP and their cross-regulation in human nasal epithelial cells (HNECs).Methods:Immunohistochemistry, quantitative RT-PCR, ELISA and Bio-Plex assay, and flow cytometry were used to detect the expression of TSLP/TSLP receptor (TSLPR)/IL-7receptor a (IL-7Ra), IL-25/IL-17B receptor (IL-17RB), and IL-33/membrane-bound ST2(ST2L)/soluble ST2(sST2) in sinonasal mucosa and HNECs. HNECs cultured at an air-liquid interface were used to explore the expression regulation of these cytokine systems.Results:Compared with controls and non-eosinophilic CRSwNP, the mRNA and protein expression of TSLP/TSLPR/IL-7Ra and ST2L/sST2, but not IL-25/IL-17RB or IL-33, were significantly increased in eosinophilic CRSwNP, predominantly in epithelial cells. The expression of TSLP, TSLPR and ST2L was positively correlated with symptom and computer tomography scan scores in eosinophilic CRSwNP and with Th2cytokine expression in sinonasal mucosa. The expression of ST2L was correlated with TSLP and its receptor expression. TSLP could induce ST2L expression that promoted IL-33-induced TSLP expression in HNECs. In addition, TSLP/TSLPR/IL-7Rct and ST2L could be induced by Th2cytokines, while IL-25/IL-17RB and IL-33could be up-regulated by Th1/Th17cytokines, in HNECs.Conclusions:The positive feedback loop between TSLP, IL-33and their receptors, and Th2cytokines may facilitate Th2-skewed inflammation in eosinophilic CRSwNP. Objective:The role of respiratory viral infection in the pathogenesis of chronic rhinosinusitis (CRS) has been rarely studied and remains controversial. The aim of this study was to explore the prevalence of respiratory viruses in the chronic status of CRS.Methods:Fifty-three control subjects, and67CRS with nasal polyp (CRSwNP) and61CRS without nasal polyp (CRSsNP) patients without signs of acute viral infection were enrolled. Epithelial cells scraped from middle nasal meatus were tested for nucleic acid of9common respiratory viruses using polymerase chain reaction assay. The clinical disease severity was compared between subjects with and without viral infection.Results:The overall detection rate of viral infection was75.47%,68.66%, and73.77%in controls, CRSwNP, and CRSsNP, respectively, and no significant difference among studied groups was observed. There was no significant difference in detection rate of any specific individual virus or multiple viruses among the groups studied either. Visual analog scale scores of symptoms, computed tomography scores, or endoscope scores did not show obvious difference between subjects with and without viral infection.Conclusions:Although a high frequency of viral infection could be observed in middle nasal meatus, no increase of frequency of viral infection could be demonstrated in chronic persistent phase of CRSsNP and CRSwNP. The contribution of the interaction between viral infection and host immunity to the pathogenesis of CRS remains to be determined.