Presentation Details
| IL-13 impairs olfactory sensory neurons and induces olfactory dysfunction in a human olfactory organoid model Ankit Chauhan1, Kang-Hoon Kim2, Michael Xiang1, James N.Palmer1, Nithin D.Adappa1, Noam A.Cohen1, Michael A.Kohanski1, Hong Wang2, Jennifer E.Douglas1. 1Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, PA, USA.2Monell Chemical Senses Center, Philadelphia, PA, USA |
Abstract
Background: Olfactory dysfunction (OD) is frequently observed in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), a condition characterized by type 2 inflammation. Although therapies targeting type 2 cytokines (IL-4, IL-5, IL-13) have been shown to improve olfaction, the underlying mechanisms remain unclear. We examined the impact of type 2 cytokines on the olfactory epithelium (OE) using a novel human olfactory organoid model. Methods: Olfactory organoids were generated from the human superior turbinate tissue of non-CRS patients. Organoids were treated with 50ng/ml IL-13 for 24 hours, 48 hours, and 7 days. Odorant (geraniol and eugenol)-evoked calcium responses were measured to assess the activity of olfactory sensory neurons (OSNs). Peak responses (F/F0) were measured and compared across groups using unpaired t-test to evaluate the effect of cytokine exposure on OSNs. Results: Exposure to IL-13 induced a significant reduction in odorant-evoked peak responses at 24 hours (p<0.0001), 48 hours (p=0.0017), and 7 days (p=0.003) timepoints compared with control cultures, indicating an impairment of OSNs. Control cultures exhibited the expected baseline response to odorants at all time points. Conclusion: Human olfactory organoids can be used to investigate downstream implications of type 2 inflammatory mediators on human OE and OD in a species-specific manner. These cytokines appear to disrupt the function of OSNs. Further investigation is warranted to better understand the role of type 2 cytokines in OD and associated changes in OE architecture and gene expression.
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