ArticleHepatology (Baltimore, Md.)2014
IL-12/Th1 and IL-23/Th17 biliary microenvironment in primary biliary cirrhosis: implications for therapy.
Article in Hepatology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.
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Who cites it
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 207 citations in OpenAlex.
- The Genomics/Genetics of Primary Biliary Cholangitis: The Case for a Functional SNP rs10893900 in ETS1/FLI1 and Review of the Literature.Clinical reviews in allergy & immunology · 2025Pooled it
- Anti-kelch-like 12 and anti-hexokinase 1: novel autoantibodies in primary biliary cirrhosis.Liver international : official journal of the International Association for the Study of the Liver · 2015Trial
- Novel Mechanistic Insights into Primary Biliary Cholangitis: From Pathogenesis to Mesenchymal Stem Cell-Mediated Repair.Biomedicines · 2026Review
- Primary Biliary Cholangitis Pathogenesis: A Pathophysiology-Based Narrative Review.International journal of molecular sciences · 2026Review
- Breaking the metabolo-immune cycle in primary biliary cholangitis for therapeutic benefit.Frontiers in immunology · 2026Review
- Molecular mechanisms underlying T cell subset imbalance and precision therapeutic targets in primary biliary cholangitis.Frontiers in pharmacology · 2026Review
- Microbiota in cholestatic diseases: crosstalk among bile composition, the biliary microbiome, and host immunity.Frontiers in immunology · 2026Review
- Article
- Peptide ES15-1 derived from Haemonchus contortus promotes goat Th17 response by regulating the STAT3/RORγt pathway.Veterinary research · 2025Article
- Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells.Cellular & molecular immunology · 2025Review
- Peripheral basophil activation: A hidden player in the immunopathogenesis of primary biliary cholangitis.World journal of hepatology · 2025Article
- Review
- The Treatment of Primary Biliary Cholangitis: Time for Personalized Medicine.Clinical reviews in allergy & immunology · 2025Review
- Innate immunity of bile and cholangiocytes in primary biliary cholangitis.Frontiers in immunology · 2025Review
- Common pathological mechanisms and therapeutic strategies in primary Sjogren's syndrome and primary biliary cholangitis: from tissue immune microenvironment to targeted therapy.Frontiers in immunology · 2025Review
- Primary biliary cholangitis has causal effects on systemic rheumatic diseases: a Mendelian randomization study.BMC gastroenterology · 2024Article
- Interleukins in liver disease treatment.World journal of hepatology · 2024Article
- Regulatory T cells in inflamed liver are dysfunctional in murine primary biliary cholangitis.Clinical and experimental immunology · 2024Article
- IL-21, not IL-17A, exacerbates murine primary biliary cholangitis.Clinical and experimental immunology · 2024Article
- Causal association of inflammatory bowel disease with sarcoidosis and the mediating role of primary biliary cholangitis.Frontiers in immunology · 2024Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 4 countries.
Funding
Abstract
unlabelledThe interleukin (IL)-12/IL-23-mediated Th1/Th17 signaling pathway has been associated with the etiopathogenesis of primary biliary cirrhosis (PBC). To address the cytokine microenvironment specifically in the liver, we examined the localized expression of cytokine subunits and their corresponding receptors using previously optimized immunohistochemistry with an extensive panel of antibodies directed at IL-12p70, IL-12p35, interferon-gamma (IFN-γ), IL-12RB2, IL-23p40, IL-23p19, IL-17, and IL-23R using liver from PBC (n = 51) and non-PBC (n = 80) control liver disease patients. Multiple portal tracts in each patient were blindly evaluated and individually scored. We report herein that although IL-12/Th1 and IL-23/Th17 staining was detected in all of the liver sections, they were primarily localized around the damaged interlobular bile ducts in PBC. Most important, Th17 skewing was prominent in advanced PBC patients with intensive secretion of IL-23p19 by inflamed hepatocytes around IL-23R, IL-12RB2, and IFN-γ expressing degenerated cholangiocytes. Our novel finding on the direct association of Th17 skewing and disease severity illustrates the significance of the IL-23/Th17 pathway in the perpetuation of IL-12/Th1-mediated immunopathology in PBC. Furthermore, localized IL-23p19 production by hepatocytes may enhance profibrotic Th17 signaling and proinflammatory IFN-γ production that contribute to PBC pathology.
conclusionOur data emphasize the pathogenic relevance of IL-12/Th1 and IL-23/Th17 in the evolution of PBC. Of significance, however, the shift from a Th1 to a Th17 imbalance at advanced stages of the disease suggests the necessity to consider modulation of the IL-23/Th17 pathway as a potential target for therapeutic intervention.
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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.