The nasal basal cell population shifts towards a diseased phenotype with impaired barrier formation capacity in allergic rhinitis

Abstract

BackgroundThe integrity of the airway epithelium is guarded by the airway basal cells that serve as progenitor cells and restore wounds in case of injury. Basal cells are a heterogenous population and specific changes in their behavior are associated with chronic barrier disruption; mechanisms that have not been studied in detail in allergic rhinitis (AR). ObjectiveWe here aim to study basal cell (sub)types in AR and healthy controls. MethodsscRNAseq of the nasal epithelium was performed on non-allergic and house dust mite allergic AR patients to reveal basal cell diversity and to identify allergy-related alterations. Flow cytometry, immunofluorescence staining and in vitro experiments using primary basal cells were performed to confirm phenotypic findings at protein level and functionally. ResultsscRNAseq, flow cytometry and immunofluorescence staining revealed that basal cells are abundantly and heterogeneously present in the nasal epithelium, suggesting specialized subtypes. The total basal cell fraction within the epithelium in AR is increased compared to controls. scRNAseq demonstrated that potentially beneficial basal cells are missing in AR epithelium, while an activated population of allergy-associated basal cells is more dominantly present. Furthermore, our in vitro proliferation, wound healing assay and ALI cultures show that AR-associated basal cells have altered progenitor capacity compared with non-allergic basal cells. ConclusionsThe nasal basal cell population is abundant, diverse and shifts towards a diseased state in AR. The absence of potentially protective subtypes and the rise of a pro-inflammatory population suggest that basal cells are important players in maintaining epithelial barrier defects in AR.