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

• 成果类型: Article
• 署名作者: Zhao, Zihe; Li, Ao; Zhu, Yan; Cen, Shaoqin; Liu, Qing; Zhang, Yuan; Fan, Hanqi; Hou, Zhenxing; Ma, Dengbin; Liu, Dingding; Duan, Maoli; Qian, Xiaoyun; Chai, Renjie; Wan, Guoqiang; Gao, Xia
• 署名单位: Nanjing University; Nanjing University; Nanjing University; Nanjing Medical University; Nanjing University; Nanjing University; Karolinska Institutet; Karolinska University Hospital; Karolinska Institutet; Southeast University - China
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12660
• DOI: 10.1073/pnas.2423240122
• 发表日期: 2025-08-12
• 关键词: inner-ear; mouse granzyme; myosin vi; expression; disorders; therapies; rantes; death

摘要

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 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 endotheof 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.