Multi-scaled transcriptomics of chronically inflamed nasal epithelium reveals immune-epithelial dynamics and tissue remodeling in nasal polyp formation.
Journal
Immunity
Journal Volume
58
Journal Issue
10
Start Page
2593
End Page
2608.e6
ISSN
1097-4180
Date Issued
2025-10-14
Author(s)
Liao, Guanrui
Nakayama, Tsuguhisa
Zhu, Bokai
Lee, Ivan T
Yeung, Jason
Yeo, Yao Yu
Chang, Yuzhou
Wang, Cankun
Liao, Steven Chun-Kang
Nkosi, Dingani
Renteria, Axel
Bravo, Dawn T
Overdevest, Jonathan B
Yan, Carol H
Zarabanda, David
Gall, Philip A
Dholakia, Sachi S
Borchard, Nicole A
Yang, Angela
Kim, Dayoung
Patel, Zara M
Hwang, Peter H
Wagh, Dhananjay
Coller, John
Phillips, Katie M
Chang, Michael T
Lechner, Matt
Li, Zihai
Nolan, Garry
Longhi, Maria Serena
Boussiotis, Vassiliki
Barouch, Dan H
Ma, Qin
Nayak, Jayakar V
Jiang, Sizun
Abstract
Chronic 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.
Subjects
autoimmunity
chronic rhinosinusitis
inflammation
nasal epithelium
nasal polyp
remodeling
single-cell
spatial transcriptomics
type 2 inflammation
SDGs
Type
journal article