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

ABSTRACT 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.