Akademik Veri Yönetim Sistemi
World Immune Regulation Meeting XVII 2023, Zürich, İsviçre, 5 Temmuz - 08 Ağustos 2023, cilt.17, sa.48, ss.67
Chronic rhinosinusitis (CRS) is a complex and heterogeneous disease characterized by persistent inflammation of the nasal cavity and nasal mucosa. It can be divided into three distinct endotypes: type 1 (T1) characterized by IFN-γ, type 2 (T2) characterized by IL-4, IL-5, and IL-13, and type 3 (T3) characterized by IL-17A. Primary human nasal epithelial cell (HNEC) organoids cultivated in a 3D culture system can provide an excellent platform for conducting high-throughput phenotypic screening and studying the pathophysiology of diseases. The objective of this study is to investigate the cellular characteristics and morphology of HNEC organoids and their response to major effector cytokines such as IFN-γ, IL-13, and IL-17A. The HNEC organoids were cultured for 18 days, and various morphological, cellular composition, and functional parameters were assessed using RT-qPCR and FITC staining. The findings revealed that the 3D HNEC organoid model effectively reproduces key features of the type 2 endotype, namely the sinus mucosa epithelia of CRS with nasal polyps when stimulated with IL-13. Following stimulation, the expression of globlet cell marker MUC5AC increased, while the ciliated and club cell markers FOXJ1 and BPIFA1 decreased. Additionally, the tight junction proteins CLDN-1 and CLDN-4 were also reduced. These results demonstrate that the 3D HNEC organoid model exhibited a decrease ciliated and club cells, along with a shift towards a mucus-producing and goblet cell-dominant phenotype, leading to the disruption of the epithelial barrier by IL-13. This model holds great potential for high throughput experimentation and the investigation of nasal epithelium morphogenesis, regeneration and development of various pathologies.