ArticleThe Journal of clinical investigation2009
Neonatal NK cells target the mouse duct epithelium via Nkg2d and drive tissue-specific injury in experimental biliary atresia.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
59 citing papers in PubMed, 109 citations in OpenAlex.
- A Phase I/IIa Trial of Intravenous Immunoglobulin Following Portoenterostomy in Biliary Atresia.Journal of pediatric gastroenterology and nutrition · 2019Trial
- Gene expression signature for biliary atresia and a role for interleukin-8 in pathogenesis of experimental disease.Hepatology (Baltimore, Md.) · 2014Trial
- Conserved Ductular Reaction Mechanisms in Biliary Atresia and Primary Sclerosing Cholangitis Derived From Single-Cell and Spatial Transcriptomics.Cellular and molecular gastroenterology and hepatology · 2026Review
- Immunology of Biliary Atresia.Seminars in pediatric surgery · 2024Review
- Jag1 insufficiency alters liver fibrosis via T cell and hepatocyte differentiation defects.EMBO molecular medicine · 2024Article
- Specific binding sites on Rhesus rotavirus capsid protein dictate the method of endocytosis inducing the murine model of biliary atresia.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Biliary atresia.Nature reviews. Disease primers · 2024Review
- Development of liver inflammatory injury in biliary atresia: from basic to clinical research.Pediatric surgery international · 2023Review
- Immune-mediated cholangiopathies in children: the need to better understand the pathophysiology for finding the future possible treatment targets.Frontiers in immunology · 2023Review
- The Impact of a CMV Infection on the Expression of Selected Immunological Parameters in Liver Tissue in Children with Biliary Atresia.Journal of clinical medicine · 2022Article
- Immunobiology of the biliary tract system.Journal of hepatology · 2022Review
- Hepatic Ly6CJournal of clinical medicine · 2022Article
- Current Understanding in the Clinical Characteristics and Molecular Mechanisms in Different Subtypes of Biliary Atresia.International journal of molecular sciences · 2022Review
- The Emerging Roles of Silver Nanoparticles to Target Viral Life Cycle and Detect Viral Pathogens.Chemistry, an Asian journal · 2022Review
- Maternal regulation of biliary disease in neonates via gut microbial metabolites.Nature communications · 2022Article
- Article
- Down-regulation of STAT3 enhanced chemokine expression and neutrophil recruitment in biliary atresia.Clinical science (London, England : 1979) · 2021Article
- Identification of Liver Immune Microenvironment-Related Hub Genes in Liver of Biliary Atresia.Frontiers in pediatrics · 2021Article
- Article
- Biliary atresia: pathology, etiology and pathogenesis.Future science OA · 2020Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Biliary atresia is a neonatal obstructive cholangiopathy that progresses to end-stage liver disease. Although the etiology is unknown, a neonatal adaptive immune signature has been mechanistically linked to obstruction of the extrahepatic bile ducts. Here, we investigated the role of the innate immune response in the pathogenesis of biliary atresia. Analysis of livers of infants at diagnosis revealed that NK cells populate the vicinity of intrahepatic bile ducts and overexpress several genes involved in cytotoxicity. Using a model of rotavirus-induced biliary atresia in newborn mice, we found that activated NK cells also populated murine livers and were the most abundant cells in extrahepatic bile ducts at the time of obstruction. Rotavirus-primed hepatic NK cells lysed cholangiocytes in a contact- and Nkg2d-dependent fashion. Depletion of NK cells and blockade of Nkg2d each prevented injury of the duct epithelium after rotavirus infection, maintained continuity of duct lumen between the liver and duodenum, and enabled bile flow, despite the presence of virus in the tissue and the overexpression of proinflammatory cytokines. These findings identify NK cells as key initiators of cholangiocyte injury via Nkg2d and demonstrate that injury to the duct epithelium drives the phenotype of experimental biliary atresia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.