Liao, GuanruiGuanruiLiaoNakayama, TsuguhisaTsuguhisaNakayamaZhu, BokaiBokaiZhuLee, Ivan TIvan TLeeYeung, JasonJasonYeungYeo, Yao YuYao YuYeoChang, YuzhouYuzhouChangWang, CankunCankunWangLiao, Steven Chun-KangSteven Chun-KangLiaoNkosi, DinganiDinganiNkosiRenteria, AxelAxelRenteriaBravo, Dawn TDawn TBravoOverdevest, Jonathan BJonathan BOverdevestYan, Carol HCarol HYanZarabanda, DavidDavidZarabandaGall, Philip APhilip AGallDholakia, Sachi SSachi SDholakiaBorchard, Nicole ANicole ABorchardYang, AngelaAngelaYangKim, DayoungDayoungKimPatel, Zara MZara MPatelHwang, Peter HPeter HHwangWagh, DhananjayDhananjayWaghColler, JohnJohnCollerPhillips, Katie MKatie MPhillipsChang, Michael TMichael TChangLechner, MattMattLechnerLi, ZihaiZihaiLiTE-HUEI YEHNolan, GarryGarryNolanLonghi, Maria SerenaMaria SerenaLonghiBoussiotis, VassilikiVassilikiBoussiotisBarouch, Dan HDan HBarouchMa, QinQinMaNayak, Jayakar VJayakar VNayakJiang, SizunSizunJiang2025-10-222025-10-222025-10-14https://scholars.lib.ntu.edu.tw/handle/123456789/732803Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease of the sinonasal cavity affecting millions worldwide. Its complex pathophysiology remains poorly understood, with emerging evidence implicating interactions between diverse immune and epithelial cells in disease progression. We applied single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics to both dissociated and intact human tissues from individuals with CRS with and without nasal polyps and compared them with controls. We revealed mechanisms of macrophage-eosinophil recruitment, CD4 and CD8 T cell dysregulation, and mast cell enrichment. We identified key immune-epithelial interactions in tissue remodeling, particularly involving basal progenitor and tuft cells. A distinct basal cell trajectory was implicated in nasal polyp formation. Orthogonal validation with spatial transcriptomics from >100 individuals with CRS revealed conserved tissue remodeling features. Our study provides insights into CRS pathophysiology, highlighting immune-epithelial interactions as potential therapeutic targets in chronic inflammation, also serving as a resource for dissecting immune disease mechanisms.enautoimmunitychronic rhinosinusitisinflammationnasal epitheliumnasal polypremodelingsingle-cellspatial transcriptomicstype 2 inflammation[SDGs]SDG3journal article10.1016/j.immuni.2025.08.00940945518