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Wang, Jun; Xu, Yanhui; Chen, Zhanghua; Liang, Jiankun; Lin, Zefeng; Liang, Huiying; Xu, Yiping; Wu, Qi; Guo, Xuanjie; Nie, Junli; Lu, Bingtai; Huang, Bing; Xian, Huifang; Wang, Xiaohui; Wu, Qiang; Zeng, Jixiao; Chai, Chengwei; Zhang, Meixue; Lin, Yuzhen; Zhang, Li; Zhao, Shanmeizi; Tong, Yanlu; Zeng, Liang; Gu, Xiaoqiong; Chen, Zhuang-gui; Yi, Shuhong; Zhang, Tong; Delfouneso, David; Zhang, Yan; Nutt, Stephen L.; Lew, Andrew M.; Lu, Liwei; Bai, Fan; Xia, Huimin; Wen, Zhe; Zhang, Yuxia
Cell, 12/2020, Letnik: 183, Številka: 7Journal Article
Biliary atresia (BA) is a severe cholangiopathy that leads to liver failure in infants, but its pathogenesis remains to be fully characterized. By single-cell RNA profiling, we observed macrophage hypo-inflammation, Kupffer cell scavenger function defects, cytotoxic T cell expansion, and deficiency of CX3CR1+effector T and natural killer (NK) cells in infants with BA. More importantly, we discovered that hepatic B cell lymphopoiesis did not cease after birth and that tolerance defects contributed to immunoglobulin G (IgG)-autoantibody accumulation in BA. In a rhesus-rotavirus induced BA model, depleting B cells or blocking antigen presentation ameliorated liver damage. In a pilot clinical study, we demonstrated that rituximab was effective in depleting hepatic B cells and restoring the functions of macrophages, Kupffer cells, and T cells to levels comparable to those of control subjects. In summary, our comprehensive immune profiling in infants with BA had educed that B-cell-modifying therapies may alleviate liver pathology. Display omitted •trans-Differentiation of cytotoxic Th17 to Th1 cells promotes liver pathology•CX3CR1+CD8Teff cells inhibit fibrosis by granzyme-mediated killing of fibroblasts•Defective induction of hepatic B cell tolerance promotes autoimmunity in infants•B-cell-modifying therapies promote immune recovery in infants with biliary atresia Liver immune profiling in infants with biliary atresia suggests B-cell-modifying therapies may alleviate liver pathology
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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