Chronic interleukin‐13 expression in mouse olfactory mucosa results in regional aneuronal epithelium. Issue 3 (23rd August 2022)

• Record Type: Journal Article
• Authors: Saraswathula, Anirudh; Liu, Melissa M.; Kulaga, Heather; Lane, Andrew P.
• Is Part Of: International forum of allergy & rhinology. Volume 13:Issue 3(2023)
• Page Start: 230
• Page End: 241
• Publication Date: 2022-08-23
• Subjects: inflammation -- interleukin 13 -- olfactory loss -- sustentacular cells; 617.51005
• DOI: 10.1002/alr.23073
• Languages: English
• ISSNs: 2042-6976

Abstract

Abstract: Background: Olfactory dysfunction is highly associated with chronic rhinosinusitis with nasal polyps (CRSwNP), 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 IL‐4/IL‐13 receptor signaling in the olfactory epithelium (OE). Methods: We created a transgenic mouse model in which IL‐13 is inducibly expressed specifically within the OE. Gene expression analysis and immunohistology were utilized to characterize the effect of IL‐13 on the structure of the OE. Results: After induction of olfactory IL‐13 expression, there is a time‐dependent loss of neurons from OE regions, accompanied by a modest inflammatory infiltrate. Horizontal basal cells undergo morphologic changes consistent with activation and demonstrate proliferation. Mucus production and increased expression of eotaxins is observed, with marked expression of Ym2 by sustentacular cells. Discussion: Chronic IL‐13 exposure has several effects on the OE that are likely to affect function. The neuronal loss 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.