The CXCL12‐CXCR4 Axis Mediates Lymphocyte Immune Overactivation in IgG4‐Related Chronic Rhinosinusitis

BACKGROUND: IgG4-related chronic rhinosinusitis (IgG4-CRS) is a new clinical entity characterized by nasal lesions; however, its pathogenesis remains unclear. This study aimed to reveal single-cell transcriptomic changes in patients with IgG4-CRS via single-cell RNA sequencing (scRNA-seq) and illustrate its pathogenesis at the single-cell level. METHODS: Nasal mucosal tissues from five patients with IgG4-CRS were used for unbiased scRNA-seq. Bioinformatic analysis was performed using these five samples and three published control samples. Immunohistochemical and multicolor immunofluorescence analyses were performed to validate the sequencing results. RESULTS: A total of 49,063 cells and 11 sub-clusters were identified. CXCL12 secretion increased in endothelial cells and fibroblasts, and CXCR4 was upregulated in the immune cells of IgG4-CRS. Enhanced chemotaxis mediated by the CXCL12-CXCR4 axis recruits excess immune cells and overactivation. Compared with those in the control group, the immunocompetence of CD4+ T cells and cytotoxicity of CD8+ T cells were enhanced in the IgG4-CRS group, and B cells were more differentiated to secrete IgG-type plasma cells. CONCLUSIONS: Chemotaxis of the CXCL12-CXCR4 axis plays a role in the pathogenesis of IgG4-CRS by influencing both the immune and nonimmune cells of IgG4-CRS.