Background: Airway basal cells are the progenitor cells within the airways and are capable of self-renewing and differentiating to multiple types of airway epithelial cells under steady-state and after injury (Ruysseveldt et al., Front. in Allergy, 2021). Recently, immune cells were shown to interact with basal cells, interfering with normal basal cell function, though this is not fully understood in upper airway diseases.

Objective: To phenotypically compare the basal cell population of controls and patients with allergic rhinitis (AR) and to investigate their response to IL-4 and histamine.

Methods: Primary nasal epithelial cells from controls and AR patients were isolated and basal cell populations were determined using scRNAseq. Sorted CD151 and CD142 double-positive basal cells were either cultured in air-liquid interface on transwell inserts or grown in culture plates and stimulated with IL-4 and histamine.

Results: scRNAseq and flow cytometry revealed that AR patients have a higher fraction of histamine receptor 1 (H1R)-expressing basal cells compared to healthy controls (5.16% vs 2.49%, p = 0.0143). No differences for IL-4 receptor expression were found. Moreover, stimulation of basal cell cultures with IL-4 (1815 vs 288 W/cm2, p<0.001) and histamine (1824 vs 1040 W/cm2, p<0.05) resulted in lower trans-epithelial electrical resistance (TEER) during differentiation and slower wound closure after injury.

Conclusion: IL-4 and histamine modulate basal cell function, delaying epithelial repair mechanisms, and basal cells from AR patients are more sensitive to histamine compared to controls. This might imply that basal cells serve as key regulators in maintaining epithelial barrier dysfunction.