Blood–labyrinth barrier damage mediated by granzymes from cytotoxic lymphocytes results in hearing loss in systemic lupus erythematosus
- Zihe Zhao
- Ao Li
- Yan Zhu
- Shaoqin Cen
- Qing Liu
- Yuan Zhang
- Hanqi Fan
- Zhenxing Hou
- Dengbin Ma
- Dingding Liu
- Maoli Duan
- Xiaoyun Qian
- Renjie Chai
- Guoqiang Wan
- Xia Gao
2025-08-12
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 HL and propose Gzmb inhibition as a potential therapeutic strategy.