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;
Publication Year 2020-11-26, Volume 183, Issue #7, Page 1867-1883e26
- Journal Title
- Publication Type
- Journal Article
- 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.
- Cell Press
- B cell haematopoiesis; Cx3cr1; Rituximab; Tnfsf13b; autoantibody; biliary atresia; cytotoxicity; hypo-inflammation; scRNA-seq; diagnosis and treatment of BA.
- WEHI Research Division(s)
- PubMed ID
- Publisher's Version
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Creation Date: 2021-02-01 12:07:33Last Modified: 2021-03-02 01:30:43