Resident Physician Johns Hopkins University School of Medicine Baltimore, Maryland
Background: Olfactory dysfunction is highly associated with chronic rhinosinusitis with nasal polyps, and the severity of loss has been linked with biomarkers of type 2 inflammation. The ability of Dupilumab to rapidly improve the sense of smell prior to improvement in polyp size suggests a direct role of IL4/IL13 receptor signaling in the olfactory epithelium.
Methods: We created a transgenic mouse model in which IL-13 is inducibly expressed specifically within the olfactory epithelium. Gene expression analysis and immunohistology were utilized to characterize the effect of IL-13 on the structure of the olfactory epithelium.
Results:After induction of olfactory IL-13, there is a regional, time-dependent loss of neurons from the olfactory epithelium. The thickness of the olfactory mucosa is maintained, but is largely devoid of neurons in areas. A modest inflammatory infiltrate accompanies the loss of neurons. Horizontal basal cells undergo morphologic changes consistent with activation, but regeneration of neurons does not occur as long as IL-13 is present.
Discussion/Conclusion: Chronic IL-13 exposure has a striking histologic effect on olfactory mucosa with development of an aneuronal epithelium. The loss of neurons with inhibition of normal regeneration is in keeping with other models of allergic type 2 nasal inflammation. Future studies are needed to correlate cellular and molecular alterations in olfactory cell populations with findings in human CRSwNP, as well as to assess olfactory function in behavioral model systems.