Abstract / Summary
Allergic Rhinitis (AR) is driven by persistent mucosal inflammation and immune imbalance. The identification of susceptibility factors, particularly genes regulating mucosal immunity, contributes to the precision treatment of AR. We performed single-cell RNA sequencing (scRNA-seq) on nasal mucosa from AR patients and healthy controls to construct a high-resolution atlas. Cellular heterogeneity, differentially expressed genes, and differentiation trajectories were analyzed, with a focused examination of ZBP1 distribution across clusters and possible mechanisms to uncover its role in allergic inflammation. scRNA-seq revealed profound shifts in nasal cellular composition in AR, notably a marked expansion of inflammatory epithelial and immune subsets. ZBP1 was strikingly upregulated in these disease-associated, pro-inflammatory clusters. Functional enrichment linked ZBP1+ cells to innate immune sensing, necroptosis, and cytokine-driven inflammatory pathways. Moreover, ZBP1+ cells actively engage in enhanced crosstalk with infiltrating immune cells, potentiating the inflammatory cascade. Inhibition of ZBP1 effectively suppresses the generation of inflammatory ARs; this was assessed using CCK8, ELISA, and PCR assays. This single-cell atlas identifies ZBP1 as a critical inflammatory sensor in AR, bridging epithelial stress to chronic mucosal inflammation. Our findings provide a clinically tractable biomarker axis for patient stratification and suggest that targeting ZBP1-centered cellular crosstalk could complement existing IgE-directed therapies.