Multi-scaled transcriptomics of chronically inflamed nasal epithelium reveals immune-epithelial dynamics and tissue remodeling in nasal polyp formation.

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.