Journal article

Liver Immune Profiling Reveals Pathogenesis and Therapeutics for Biliary Atresia

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 Show all

CELL | CELL PRESS | Published : 2020

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, 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 st..

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Grants

Awarded by National Natural Science Foundation of China


Awarded by National Science and Technology Major Project


Awarded by Integration Project of Major Research Plan of China


Awarded by Key-Area Research and Development Program of Guangdong Province, China


Awarded by Guangzhou Women and Children's Medical Center Fund


Awarded by Chongqing International Institute for Immunology


Awarded by National Health and Medical Research Council of Australia


Funding Acknowledgements

The National Natural Science Foundation of China (91742109, 31770978, 81971430, 81771629, and 91842304), National Science and Technology Major Project (2018ZX10302205 and 2019YFC1315702), Integration Project of Major Research Plan of China (91842304), Key-Area Research and Development Program of Guangdong Province, China (2019B0020227001), Guangzhou Women and Children's Medical Center Fund (5001-3001032 and 5001-3001082), Chongqing International Institute for Immunology (2020YJC10) and National Health and Medical Research Council of Australia (1105209, 1143976, and 1150425 to A.M.L.) funded this study.