Interaction between airway basal cells, mast cells and type 2 immunity contributes to epithelial barrier dysfunction in allergic rhinitis

Abstract

Basal cell dysfunction contributes to the pathophysiology of chronic inflammatory airway disorders and is linked to persistent epithelial barrier defects. Epithelial integrity dysfunction, basal cell hyperplasia and metaplasia have been described in allergic rhinitis (AR). However, it remains unclear how basal cell progenitor functions are regulated and if basal cells contribute to type 2 inflammatory responses. Here, we report on the proinflammatory and sensory role of basal cells in AR. Using primary nasal basal cells from controls and AR patients, we demonstrate that Der p1 induces basal cell cytokine (IL-6) and chemokine (CXCL1, CXCL6, CXCL8, SCF) expression and/or release via PAR2, suggesting a role for basal cells as environmental sensors and inflammatory regulators. Using nasal biopsies, we show that mast cells are attracted to the epithelium in AR, likely via basal cell-derived SCF, and induce basal cell chemokine (CCL26, CXCL1, CXCL6, SCF) release via histamine and tryptase in vitro. Finally, histamine, IL-4 and IL-13 impair primary nasal basal cell proliferation, mobility, barrier formation, and differentiation in in vitro cellular assays, illustrating basal cell dysfunction in AR.