Blood-labyrinth barrier damage mediated by granzymes from cytotoxic lymphocytes results in hearing loss in systemic lupus erythematosus.

ABSTRACT: Hearing loss (HL) in patients with systemic lupus erythematosus (SLE) has been widely reported, though the underlying mechanisms remain unclear. In this study, we demonstrate significant HL in an imiquimod-induced mouse model of SLE, accompanied by blood-labyrinth barrier (BLB) damage in the stria vascularis (SV). We found that cytotoxic CD8⁺ T lymphocytes and natural killer cells mediate BLB disruption, with granzyme b (Gzmb) acting as the primary factor inducing cell death of the cochlear capillary endothelial cells. Remarkably, inhibiting Gzmb by Serpinb9 significantly alleviates the elevations of hearing thresholds in imiquimod-induced SLE model mice, suggesting a therapeutic target for autoimmune-related HL. Our findings provide insights into the pathogenesis of SLE-related

SUBMITTER: Zhao Z 

PROVIDER: S-EPMC12377648 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature