ArticleThe Journal of clinical investigation2014
Biliary repair and carcinogenesis are mediated by IL-33-dependent cholangiocyte proliferation.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
What it found
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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
115 citing papers in PubMed, 197 citations in OpenAlex.
- A Phase I/IIa Trial of Intravenous Immunoglobulin Following Portoenterostomy in Biliary Atresia.Journal of pediatric gastroenterology and nutrition · 2019Trial
- Non-Invasive Biomarkers for Assessing Liver Fibrosis in Biliary Atresia: A Literature Review.International journal of molecular sciences · 2026Review
- The Dual Roles of Gut Microbiota in Biliary Atresia: Mechanisms, Biomarker Potential, and Therapeutic Implications.Microorganisms · 2026Review
- IDH1 Mutant Glioma Favors Group 3 Innate Lymphoid Cells and Is Resistant to Immune Checkpoint Expression.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Cholangiocarcinoma 2026: status quo, unmet needs and priorities.Nature reviews. Gastroenterology & hepatology · 2026Review
- Critical role of interleukin-33 in pathogenesis and progression of metabolic dysfunction-associated steatotic liver disease.Frontiers in medicine · 2026Review
- Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells.Cellular & molecular immunology · 2025Review
- Microenvironmental control of the ductular reaction: balancing repair and disease progression.Cell death & disease · 2025Review
- Portal Fibrosis and the Ductular Reaction: Pathophysiological Role in the Progression of Liver Disease and Translational Opportunities.Gastroenterology · 2025Review
- Review
- Interplay ofFrontiers in cardiovascular medicine · 2025Article
- Innovation through imitation: IL-33 decoys show promise in pulmonary fibrosis.The Journal of pharmacology and experimental therapeutics · 2025Article
- Biliary stents for active materials and surface modification: Recent advances and future perspectives.Bioactive materials · 2024Review
- Aberrant differentiation and proliferation of hepatocytes in chronic liver injury and liver tumors.Pathology international · 2024Review
- Review
- Treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis: a comprehensive review.eGastroenterology · 2024Review
- Interleukin-13 (IL-13)-A Pleiotropic Cytokine Involved in Wound Healing and Fibrosis.International journal of molecular sciences · 2023Review
- Programmed cell death-1 receptor-mediated regulation of TbetProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Interleukin-33 as a Potential Therapeutic Target in Gastric Cancer Patients: Current Insights.OncoTargets and therapy · 2023Review
- Relationship between the expression levels of CD4+ T cells, IL-6, IL-8 and IL-33 in the liver of biliary atresia and postoperative cholangitis, operative age and early jaundice clearance.Pediatric surgery international · 2022Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Injury to the biliary epithelium triggers inflammation and fibrosis, which can result in severe liver diseases and may progress to malignancy. Development of a type 1 immune response has been linked to biliary injury pathogenesis; however, a subset of patients with biliary atresia, the most common childhood cholangiopathy, exhibit increased levels of Th2-promoting cytokines. The relationship among different inflammatory drivers, epithelial repair, and carcinogenesis remains unclear. Here, we determined that the Th2-activating cytokine IL-33 is elevated in biliary atresia patient serum and in the livers and bile ducts of mice with experimental biliary atresia. Administration of IL-33 to WT mice markedly increased cholangiocyte proliferation and promoted sustained cell growth, resulting in dramatic and rapid enlargement of extrahepatic bile ducts. The IL-33-dependent proliferative response was mediated by an increase in the number of type 2 innate lymphoid cells (ILC2s), which released high levels of IL-13 that in turn promoted cholangiocyte hyperplasia. Induction of the IL-33/ILC2/IL-13 circuit in a murine biliary injury model promoted epithelial repair; however, induction of this circuit in mice with constitutive activation of AKT and YAP in bile ducts induced cholangiocarcinoma with liver metastases. These findings reveal that IL-33 mediates epithelial proliferation and suggest that activation of IL-33/ILC2/IL-13 may improve biliary repair and disruption of the circuit may block progression of carcinogenesis.
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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.