Th2 cytokines orchestrate the secretion of MUC 5 AC and MUC 5B in IL‐5‐positive chronic rhinosinusitis with nasal polyps

Y Zhang, L Derycke, G Holtappels, XD Wang, L Zhang… - Allergy, 2019 - Wiley Online Library
Y Zhang, L Derycke, G Holtappels, XD Wang, L Zhang, C Bachert, N Zhang
Allergy, 2019Wiley Online Library
Background Mucin over‐secretion is a significant characteristic of chronic rhinosinusitis with
nasal polyps (CRS w NP). This study aimed to investigate the relationship between Th2
cytokines and MUC 5 AC or MUC 5B, and the mechanism of mucin over‐secretion in the
type‐2 inflammatory endotype of CRS w NP. Methods Main Th‐cell cytokines, associated
mediators, and mucins were determined in the homogenates of nasal polyp samples from
21 CRS w NP patients and inferior turbinate samples from 8 controls, by ELISA or Uni CAP …
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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