广州医科大学张玉霞等研究人员利用肝脏免疫分析揭示胆道闭锁的发病机理和治疗方法。2020年11月27日，《细胞》杂志在线发表了这项成果。

Title: Liver Immune Profiling Reveals Pathogenesis and Therapeutics for Biliary Atresia

Author: Jun Wang, Yanhui Xu, Zhanghua Chen, Jiankun Liang, Zefeng Lin, Huiying Liang, Yiping Xu, Qi Wu, Xuanjie Guo, Junli Nie, Bingtai Lu, Bing Huang, Huifang Xian, Xiaohui Wang, Qiang Wu, Jixiao Zeng, Chengwei Chai, Meixue Zhang, Yuzhen Lin, Li Zhang, Shanmeizi Zhao, Yanlu Tong, Liang Zeng, Xiaoqiong Gu, Zhuang-gui Chen, Shuhong Yi, Tong Zhang, David Delfouneso, Yan Zhang, Stephen L. Nutt, Andrew M. Lew, Liwei Lu, Fan Bai, Huimin Xia, Zhe Wen, Yuxia Zhang

Issue&Volume: 2020-11-27

Abstract: 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, wediscovered that hepatic B cell lymphopoiesis did not cease after birth and that tolerancedefects contributed to immunoglobulin G (IgG)-autoantibody accumulation in BA. Ina rhesus-rotavirus induced BA model, depleting B cells or blocking antigen presentationameliorated liver damage. In a pilot clinical study, we demonstrated that rituximabwas 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-modifyingtherapies may alleviate liver pathology.

DOI: 10.1016/j.cell.2020.10.048

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31455-0