Liver immune profiling reveals pathogenesis and therapeutics for biliary atresia
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.
WEHI Research Division(s)
Immunology
PubMed ID
33248023
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
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