Journal article
Liver Immune Profiling Reveals Pathogenesis and Therapeutics for Biliary Atresia
J Wang, Y Xu, Z Chen, J Liang, Z Lin, H Liang, Y Xu, Q Wu, X Guo, J Nie, B Lu, B Huang, H Xian, X Wang, Q Wu, J Zeng, C Chai, M Zhang, Y Lin, L 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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Awarded by National Health and Medical Research Council
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.