Ferritin triggers neutrophil extracellular trap-mediated cytokine storm through Msr1 contributing to adult-onset Still's disease pathogenesis.
Ferritin triggers neutrophil extracellular trap-mediated cytokine storm through Msr1 contributing to adult-onset Still's disease pathogenesis.
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铁蛋白通过 Msr1 触发中性粒细胞胞外陷阱介导的细胞因子风暴，导致成人斯蒂尔病发病机制
DOI：
10.1038/s41467-022-34560-7
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发表时间：
2022-11-10
影响因子：
16.6
通讯作者：
Hu, Qiongyi
中科院分区：
文献类型：
--
作者：
Jia, Jinchao;Wang, Mengyan;Meng, Jianfen;Ma, Yuning;Wang, Yang;Miao, Naijun;Teng, Jialin;Zhu, Dehao;Shi, Hui;Sun, Yue;Liu, Honglei;Cheng, Xiaobing;Su, Yutong;Ye, Junna;Chi, Huihui;Liu, Tingting;Zhou, Zhuochao;Wan, Liyan;Chen, Xia;Wang, Fan;Zhang, Hao;Ben, Jingjing;Wang, Jing;Yang, Chengde;Hu, Qiongyi
高铁蛋白综合征是一种压倒性的炎症状况，其特征是铁蛋白水平高，全身注射和多器官功能障碍，但是铁蛋白的致病作用在这里仍然未知。肝组织中的中性粒细胞白细胞浸润和中性粒细胞外陷阱（净）形成。铁蛋白诱导的净形成取决于肽基金蛋白脱节酶4和中性粒细胞弹性酶的表达，以及有力性氧的产生。净形成途径。动物模型的相关性被观察到增强的净形成，增加的MSR1表达和对中性粒细胞白细胞的信号传导也是成人发病的静止病（AOSD）的特征，这是一种典型的高精综合征。网络介导的细胞因子风暴中的铁蛋白，并建议靶向网或MSR1可能使AOSD患者受益。
高铁蛋白综合征是一组由高铁蛋白水平的严重炎症疾病的集体术语，包括成人发作的静止病和Covid-19一种致病因子，可触发中性粒细胞白细胞激活和细胞外陷阱形成。
Hyperferritinemic syndrome, an overwhelming inflammatory condition, is characterized by high ferritin levels, systemic inflammation and multi-organ dysfunction, but the pathogenic role of ferritin remains largely unknown. Here we show in an animal model that ferritin administration leads to systemic and hepatic inflammation characterized by excessive neutrophil leukocyte infiltration and neutrophil extracellular trap (NET) formation in the liver tissue. Ferritin-induced NET formation depends on the expression of peptidylarginine deiminase 4 and neutrophil elastase and on reactive oxygen species production. Mechanistically, ferritin exposure increases both overall and cell surface expression of Msr1 on neutrophil leukocytes, and also acts as ligand to Msr1 to trigger the NET formation pathway. Depletion of neutrophil leukocytes or ablation of Msr1 protect mice from tissue damage and the hyperinflammatory response, which further confirms the role of Msr1 as ferritin receptor. The relevance of the animal model is underscored by the observation that enhanced NET formation, increased Msr1 expression and signalling on neutrophil leukocytes are also characteristic to adult-onset Still’s disease (AOSD), a typical hyperferritinemic syndrome. Collectively, our findings demonstrate an essential role of ferritin in NET-mediated cytokine storm, and suggest that targeting NETs or Msr1 may benefit AOSD patients.
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影响因子：
27.4
作者：
Knight JS;Subramanian V;O'Dell AA;Yalavarthi S;Zhao W;Smith CK;Hodgin JB;Thompson PR;Kaplan MJ
通讯作者：
Kaplan MJ
影响因子：
28.2
作者：
Liu, Yuwei;Du, Xuebei;Zhao, Yan
通讯作者：
Zhao, Yan
影响因子：
4.4
作者：
Jamilloux, Yvan;Gerfaud-Valentin, Mathieu;Seve, Pascal
通讯作者：
Seve, Pascal
DOI：
10.1093/rheumatology/keaa368
发表时间：
2021-01-05
期刊：
Rheumatology (Oxford, England)
影响因子：
--
作者：
Jia J;Yang L;Cao Z;Wang M;Ma Y;Ma X;Liu Q;Teng J;Shi H;Liu H;Cheng X;Ye J;Su Y;Sun Y;Chi H;Liu T;Wang Z;Wan L;Yang C;Hu Q
通讯作者：
Hu Q
DOI：
10.1073/pnas.1809028115
发表时间：
2018-11-27
影响因子：
11.1
作者：
Chen, Zhaochun;Diaz, Giacomo;Farci, Patrizia
通讯作者：
Farci, Patrizia