Role of IFN‐γ, IL‐13, and IL‐17 on mucociliary differentiation of nasal epithelial cells in chronic rhinosinusitis with nasal polyps

Summary Background Mucociliary dysfunction is a prominent pathophysiological feature of chronic rhinosinusitis with nasal polyps ( CRS w NP ); however, the precise mechanisms underlying mucociliary dysfunction are still unclear. Objective The aim of this study was therefore to evaluate the effects of IFN ‐γ, IL ‐13, and IL ‐17 on human nasal mucociliary differentiation and ciliary beat frequency ( CBF ) in patients with CRS w NP . Methods Human nasal epithelial cells from tissue of patients with CRS w NP and control subjects were established as air–liquid interface ( ALI ) primary cultures. Confluent cultures were incubated with10 ng/mL each of IFN ‐γ, IL ‐13, or IL ‐17 for 14 days and assessed for expression of specific morphological markers and factors associated with mucociliary differentiation, the percentage of ciliated and goblet cells, and CBF . Results In comparison with control subjects, percentage of ciliated cells and CBF were decreased; while percentage of goblet cells, FOXJ 1, and MUC 5 AC mRNA expression were increased in nasal polyp‐derived epithelial cultures. Treatment with IFN ‐γ and IL ‐13 significantly decreased the expression of β‐tubulin IV (specific cilia marker), ciliated cell number, and expression of FOXJ 1 and DNAI 2 , in epithelial cultures derived from both CRS w NP patients and control subjects. Furthermore, while both IFN ‐γ and IL ‐13 treatment significantly decreased the CBF of cells from both CRS w NP patients and control subjects, IL ‐13 additionally significantly increased goblet cell number and the expression of MUC 5 AC and CLCA 1 , in these cultures. IL ‐17 treatment did not significantly affect ciliated or goblet cell differentiation, CBF , nor MUC 5 AC and CLCA 1 expression, but increased both MUC 5B mRNA and protein expression in these cultures. Conclusion and clinical relevance The demonstration that IFN ‐γ and IL ‐13 both significantly reduce ciliated cell differentiation and CBF in CRS w NP patients, and IL ‐13 additionally induces significant goblet cell hyperplasia and MUC 5 AC mucin expression, as well as IL ‐17 significantly increases MUC 5B mucin expression, suggests that these inflammatory cytokines may be potential therapeutic targets in the management of CRS w NP .