Neutrophil extracellular traps promote ΔNp63+ basal cell hyperplasia in chronic rhinosinusitis.
J Allergy Clin Immunol
; 153(3): 705-717.e11, 2024 Mar.
Article
en En
| MEDLINE
| ID: mdl-38000697
ABSTRACT
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sinusitis
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Rinitis
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Pólipos Nasales
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Trampas Extracelulares
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Rinosinusitis
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Allergy Clin Immunol
Año:
2024
Tipo del documento:
Article