科學家揭示膽道閉鎖的發病機理和治療方法
作者：
小柯機器人發布時間：2020/11/30 16:56:14
廣州醫科大學張玉霞等研究人員利用肝臟免疫分析揭示膽道閉鎖的發病機理和治療方法。2020年11月27日，《細胞》雜誌在線發表了這項成果。
通過單細胞RNA譜分析，研究人員觀察到膽道閉鎖（BA）患兒的巨噬細胞低炎症、庫普弗細胞清除功能缺陷、細胞毒性T細胞擴增以及CX3CR1+效應T和自然殺傷（NK）細胞缺乏。更重要的是，研究人員發現出生後肝B細胞淋巴細胞減少並沒有停止，並且耐受缺陷導致免疫球蛋白G（IgG）-自身抗體在BA中積累。在恆河猴輪狀病毒誘導的BA模型中，消耗B細胞或阻斷抗原呈遞可減輕肝損傷。
在一項初步的臨床研究中，研究人員證明了利妥昔單抗可有效清除肝B細胞並將巨噬細胞、庫普弗細胞和T細胞的功能恢復到與對照組相當的水平。總而言之，對BA嬰兒的全面免疫分析表明，B細胞修飾療法可以緩解肝臟病理。
據悉，BA是一種嚴重的膽管疾病，可導致嬰兒肝衰竭，但其發病機理仍有待充分表徵。
附：英文原文
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
Cell：《細胞》，創刊於1974年。隸屬於細胞出版社，最新IF：36.216