Liver immune profiling reveals pathogenesis and therapeutics for biliary atresia

Wang, J; Xu, Y; Chen, Z; Liang, J; Lin, Z; Liang, H; Wu, Q; Guo, X; Nie, J; Lu, B; Huang, B; Xian, H; Wang, X; Zeng, J; Chai, C; Zhang, M; Lin, Y; Zhang, L; Zhao, S; Tong, Y; Zeng, L; Gu, X; Chen, ZG; Yi, S; Zhang, T; Delfouneso, D; Zhang, Y; Nutt, SL; Lew, AM; Lu, L; Bai, F; Xia, H; Wen, Z

Author(s): Wang, J; Xu, Y; Chen, Z; Liang, J; Lin, Z; Liang, H; Wu, Q; Guo, X; Nie, J; Lu, B; Huang, B; Xian, H; Wang, X; Zeng, J; Chai, C; Zhang, M; Lin, Y; Zhang, L; Zhao, S; Tong, Y; Zeng, L; Gu, X; Chen, ZG; Yi, S; Zhang, T; Delfouneso, D; Zhang, Y; Nutt, SL; Lew, AM; Lu, L; Bai, F; Xia, H; Wen, Z;
Details: Publication Year 2020-11-26,Volume 183,Issue #7,Page 1867-1883e26
Journal Title: Cell
Publication Type: Journal Article
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 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.
Publisher: Cell Press
Keywords: B cell haematopoiesis; Cx3cr1; Rituximab; Tnfsf13b; autoantibody; biliary atresia; cytotoxicity; hypo-inflammation; scRNA-seq; diagnosis and treatment of BA.
Research Division(s): Immunology
PubMed ID: 33248023
Publisher's Version: https://doi.org/10.1016/j.cell.2020.10.048
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2021-02-01 12:07:33

Last Modified: 2021-03-02 01:30:43