Eosinophil cationic protein-driven type 2 inflammation impairs olfactory function in a murine model.

Abstract

Objective and design: Eosinophilic chronic rhinosinusitis (ECRS) is characterized by the infiltration of eosinophils and is frequently associated with olfactory dysfunction (OD). The underlying mechanisms of OD related to ECRS remain poorly understood. This study aims to develop a murine model of eosinophil-induced OD (EIOD) within a brief timeframe by administering eosinophil cationic protein (ECP) intranasally. The efficacy of the model was assessed through a series of behavioral, morphological, and molecular biology experiments.

Methods: Male mice received intranasal ECP for durations of 10 and 20 days to induce EIOD. The established mouse model was subsequently subjected to olfactory behavior assessments, histological examinations, cytokine analysis of nasal lavage fluid, and gene expression profiling to confirm its validity.

Results: Behavioral assessments conducted on the mice substantiated the presence of OD and revealed a thinning of the olfactory epithelial mucosa, accompanied by a reduction in the number of olfactory sensory neurons. Concurrently, an increase in type 2 inflammatory cytokines was detected in the nasal lavage fluid. Upon cessation of ECP administration, both olfactory function and the olfactory mucosa exhibited signs of recovery. Furthermore, RNA sequencing analysis revealed alterations in certain inflammatory immune pathways.

Conclusion: This study effectively established and validated an EIOD murine model, thereby offering valuable tools for investigating the pathogenesis and potential therapeutic interventions for this disease.