Neutrophil extracellular traps promote ΔNp63+ basal cell hyperplasia in chronic rhinosinusitis

Background

Neutrophil extracellular traps (NETs) are observed in chronic rhinosinusitis (CRS), although their role remains unclear.

Objectives

This study aimed to investigate the influence of NETs on the CRS epithelium.

Methods

Forty-five sinonasal biopsy specimens were immunofluorescence-stained to identify NETs and p63⁺ basal stem cells. Investigators treated human nasal epithelial cells with NETs and studied them with immunofluorescence staining, Western blotting, and quantitative real-time PCR. NET inhibitors were administered to a murine neutrophilic nasal polyp model.

Results

NETs existed in tissues in patients with CRS with nasal polyps, especially in noneosinophilic nasal polyp tissues. p63⁺ basal cell expression had a positive correlation with the release of NETs. NETs induced the expansion of Ki-67⁺p63⁺ cells. We found that ΔNp63, an isoform of p63, was mainly expressed in the nasal epithelium and controlled by NETs. Treatment with deoxyribonuclease (DNase) I or Sivelestat (NET inhibitors) prevented the overexpression of ΔNp63+ epithelial stem cells and reduced polyp formation.

Conclusions

These results reveal that NETs are implicated in CRS pathogenesis via basal cell hyperplasia. This study suggests a novel possibility of treating CRS by targeting NETs.