The Journal of clinical investigation · 2026
IL-6 receptor blockade impedes proinflammatory atypical Treg subset associated with immune checkpoint inhibitor-induced inflammatory arthritis.
СтатьяНазвание и аннотация: Перевод в очереди
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Ma Yifei, Liu Nianqi, Li Yan, Zhang Denghan, He Shaohui, Lv Jun, Jiang Yongluo, Jian Guangmin, Zhang Jingyao, Zhu Pengfei, Ma Yue, Lin Jiacai, Li Jin, Wu Tong, Xu Yiwei, Lyu Xiajie, Wang Youlong, Li Yiming, Niu Yu Si, Guo Zhenyun, Lin Churong, Fang Ningnan, Jiang Wei, Wang Lihong, Yuan Mengqin, Wang Shenyue, Huang Shulin, Huang Qi, Li Jinjian, Lu Jun, Chen Bocen, Zhong Guanqing, Liu Haizhou, Ding Fadian, Weng Shangeng, Li Rui, Zhang Ao
Аннотация
BACKGROUNDImmune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) significantly impairs cancer therapy and patient quality of life, yet its pathogenic mechanisms remain unclear.METHODSThrough integrated single-cell multi-omics analysis of paired peripheral blood, synovial fluid, and tumor samples from longitudinal ICI-IA cohorts and matched controls, we identified a unique regulatory T-cell (Treg) population coexpressing CD137 and IL-6R (AtpTreg).RESULTSThese cells exhibited reduced immunosuppressive capacity while aberrantly producing high levels of IL-17 and promoting proinflammatory responses of synoviocytes. AtpTreg exhibits shared clonotypes and phenotypes across tissue compartments. Notably, AtpTreg frequency correlates with increased arthritis severity yet paradoxically associates with improved overall survival. Anti-IL6R therapy reduced AtpTreg levels, corresponding with improved arthritis outcomes and quality of life, without compromising anti-tumor immunity.CONCLUSIONOur findings define a pathogenic Treg subset in ICI-IA and validate IL-6R blockade as a mechanism-based therapeutic strategy, bridging mechanistic discovery to clinical translation.TRIAL REGISTRATIONNCT07357636.FUNDINGThe National Natural Science Foundation of China General Fund Project; National Natural Science Foundation of China Youth Science Fund Project; Regional joint key support project of National Natural Science Foundation of China; Natural Science Foundation of Fujian Province; Joint Funds for the Innovation of Science and Technology, Fujian Province.