Th2 cytokines orchestrate the secretion of MUC5AC and MUC5B in IL-5-positive chronic rhinosinusitis with nasal polyps.

BACKGROUND:Mucin over-secretion is a significant characteristic of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to investigate the relationship between Th2 cytokines and MUC5AC or MUC5B, and the mechanism of mucin over-secretion in the type-2 inflammatory endotype of CRSwNP. METHODS:Main Th-cell cytokines, associated mediators, and mucins were determined in the homogenates of nasal polyp samples from 21 CRSwNP patients and inferior turbinate samples from 8 controls, by ELISA or UniCAP system. Secretion of MUC5AC and MUC5B was measured in the supernatants of IL-5, IL-4, or IL-13 primed nasal polyp fragments. Co-localization of MUC5AC, MUC5B, and IL-4 receptor α (IL-4Rα) in CRSwNP and controls was evaluated by immunohistochemistry. Gene expression of IL-4Rα in the samples was measured by real-time reverse transcription-polymerase chain reaction. RESULTS:Baseline protein levels of the Th2-cytokines IL-4, IL-5, and IL-13, and mucins MUC5AC and MUC5B were significantly higher in the IL-5(+) CRSwNP group, compared to control and IL-5(-) CRSwNP groups. MUC5AC and MUC5B secretions were significantly increased in IL-4- or IL-13-primed, but not IL-5-primed fragments of nasal polyps. Immuno-stained serial sections demonstrated that IL-4Rα was widely expressed in the epithelium and submucosal glands in control and nasal polyp tissues. Gene expression of IL-4Rα was elevated in nasal polyp tissues, specifically in the IL-5(+) CRSwNP group. CONCLUSIONS:In type-2 inflammatory nasal polyps, characterized by the tissue expression of IL-5, MUC5AC and MUC5B are overexpressed. Both IL-4 and IL-13 may upregulate mucin expression via IL-4Rα, which is also overexpressed in IL-5(+) CRSwNP.

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