Interaction of thymic stromal lymphopoietin, IL‐33, and their receptors in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps

Abstract Background Thymic stromal lymphopoietin ( TSLP ), IL ‐25, and IL ‐33 system contribute to the initiation and development of Th2 responses. This study aimed to explore the involvement of TSLP , IL ‐25, IL ‐33, and their receptors in type 2 T‐helper (Th) responses in chronic rhinosinusitis with nasal polyps ( CRS w NP s) and their cross‐regulation in human nasal epithelial cells ( HNEC s). Methods Immunohistochemistry, quantitative RT ‐ PCR , ELISA , Bio‐Plex assay, and flow cytometry were used to detect the expression of TSLP /common γ‐like TSLP receptor ( TSLPR )/ IL ‐7 receptor α ( IL ‐7Rα), IL ‐25/ IL ‐17B receptor ( IL ‐17 RB ), and IL ‐33/membrane‐bound ST 2 ( ST 2L)/soluble ST 2 ( sST 2) in sinonasal mucosa and HNEC s. HNEC s cultured at an air–liquid interface were used to explore the expression in regulation of these cytokine systems. Results Compared with controls and noneosinophilic CRS w NP , the expression of TSLP / TSLPR / IL ‐7Rα and ST 2L/ sST 2 was significantly increased in eosinophilic CRS w NP , predominantly in epithelial cells. In contrast, the expression of IL ‐33 and IL ‐25/ IL ‐17 RB was enhanced in epithelial cells in both eosinophilic and noneosinophilic CRS w NP compared to controls. The expression of TSLP , TSLPR , and ST 2L was positively correlated with symptom and computer tomography scan scores in eosinophilic CRS w NP and with Th2 cytokine expression in sinonasal mucosa. The expression of ST 2L was correlated with TSLP and its receptor expression. TSLP could induce ST 2L expression that promoted IL ‐33‐induced TSLP expression in HNEC s. In addition, TSLP / TSLPR / IL ‐7Rα and ST 2L could be induced by Th2 cytokines, while IL ‐25/ IL ‐17 RB and IL ‐33 could be upregulated by Th1/Th17 cytokines, in HNEC s. Conclusions The positive feedback loop between TSLP , IL ‐33 and their receptors, and Th2 cytokines may facilitate Th2‐skewed inflammation in eosinophilic CRS w NP .