File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Liver Immune Profiling Reveals Pathogenesis and Therapeutics for Biliary Atresia

TitleLiver Immune Profiling Reveals Pathogenesis and Therapeutics for Biliary Atresia
Authors
Keywordsbiliary atresiasc
RNA-seq
cytotoxicity
CX3CR1
B cell haematopoiesis
Issue Date2020
PublisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/cell
Citation
Cell, 2020, v. 183 n. 7, p. 1867-1883.e26 How to Cite?
AbstractBiliary 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.
Persistent Identifierhttp://hdl.handle.net/10722/304803
ISSN
2023 Impact Factor: 45.5
2023 SCImago Journal Rankings: 24.342
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, J-
dc.contributor.authorXu, Y-
dc.contributor.authorChen, Z-
dc.contributor.authorLiang, J-
dc.contributor.authorLin, Z-
dc.contributor.authorLiang, H-
dc.contributor.authorXu, Y-
dc.contributor.authorWu, Q-
dc.contributor.authorGuo, X-
dc.contributor.authorNie, J-
dc.contributor.authorLu, B-
dc.contributor.authorHuang, B-
dc.contributor.authorXian, H-
dc.contributor.authorWang, X-
dc.contributor.authorWu, Q-
dc.contributor.authorZeng, J-
dc.contributor.authorChai, C-
dc.contributor.authorZhang, M-
dc.contributor.authorLin, Y-
dc.contributor.authorZhang, L-
dc.contributor.authorZhao, S-
dc.contributor.authorTong, Y-
dc.contributor.authorZeng, L-
dc.contributor.authorGu, X-
dc.contributor.authorChen, Z-
dc.contributor.authorYi, S-
dc.contributor.authorZhang, T-
dc.contributor.authorDelfounes, D-
dc.contributor.authorZhang, Y-
dc.contributor.authorNutt, SL-
dc.contributor.authorLew, AM-
dc.contributor.authorLu, L-
dc.contributor.authorBai, F-
dc.contributor.authorXia, H-
dc.contributor.authorWen, Z-
dc.contributor.authorZhang, Y-
dc.date.accessioned2021-10-05T02:35:25Z-
dc.date.available2021-10-05T02:35:25Z-
dc.date.issued2020-
dc.identifier.citationCell, 2020, v. 183 n. 7, p. 1867-1883.e26-
dc.identifier.issn0092-8674-
dc.identifier.urihttp://hdl.handle.net/10722/304803-
dc.description.abstractBiliary 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.-
dc.languageeng-
dc.publisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/cell-
dc.relation.ispartofCell-
dc.subjectbiliary atresiasc-
dc.subjectRNA-seq-
dc.subjectcytotoxicity-
dc.subjectCX3CR1-
dc.subjectB cell haematopoiesis-
dc.titleLiver Immune Profiling Reveals Pathogenesis and Therapeutics for Biliary Atresia-
dc.typeArticle-
dc.identifier.emailLu, L: liweilu@hku.hk-
dc.identifier.authorityLu, L=rp00477-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.cell.2020.10.048-
dc.identifier.pmid33248023-
dc.identifier.scopuseid_2-s2.0-85097477505-
dc.identifier.hkuros326199-
dc.identifier.volume183-
dc.identifier.issue7-
dc.identifier.spage1867-
dc.identifier.epage1883.e26-
dc.identifier.isiWOS:000602900800011-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats