Abstract
BACKGROUND: Recent studies have shown that solitary chemosensory cells (SCCs) are rare nasal epithelial cells effectively responding to pathogens and are the predominant epithelial sources of IL-25. We investigated the roles of SCCs in nasal eosinophilic inflammation in house dust mite (HDM)-sensitized allergic rhinitis (AR). METHODS: Epithelial phenotypes were detected in nasal mucosal specimens from control participants and HDM-AR patients. Differentiated human nasal epithelial cells (hNECs) were exposed to HDM extract Dermatophagoides pteronissinus (Derp), with or without a Protease-activated receptor (PAR-2) antagonist, and epithelial phenotypes were characterized. IL-25 receptor (IL-17RA and IL-17RB) expression in eosinophils was analyzed in human nasal mucosal cells (hNMCs). Finally, the expression of PAR-2 and POU domain class 2 transcription factor 3 (POU2F3) in SCCs within human nasal mucosal epithelium was evaluated. RESULTS: POU2F3(+) SCCs and MUC5AC(+) goblet cells were enriched in the nasal mucosa, along with elevated IL-25 levels in the nasal secretions of HDM-AR patients. Exposure of hNECs to Derp increased SCCs expansion and mucin production. Moreover, IL-25 protein potently promoted mucin production in hNECs and IL-25 receptor expression in eosinophils of hNMCs. PAR-2 expression was significantly enhanced in Derp-exposed hNECs, and inhibiting PAR-2 activation reversed the Derp-induced effects in hNECs and hNMCs. Finally, PAR-2 expression levels significantly increased in nasal epithelium from HDM-AR patients, correlating with POU2F3(+) SCCs density and nasal eosinophil percentage. CONCLUSIONS: These findings demonstrated that SCCs could sense HDM and produce IL-25, triggering mucin overproduction and eosinophilic IL-25 receptor expression via PAR-2 activation, which suggesting that SCCs might be powerful immunomodulators of nasal eosinophilic inflammation in HDM-AR.