ArticleGut2021
Neutrophils interact with cholangiocytes to cause cholestatic changes in alcoholic hepatitis.
Article in Gut, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- Cholestasis in Alcohol-Associated Liver Disease.The American journal of pathology · 2026Review
- Central role for cholangiocyte pathobiology in cholestatic liver diseases.Hepatology (Baltimore, Md.) · 2025Review
- Portal Fibrosis and the Ductular Reaction: Pathophysiological Role in the Progression of Liver Disease and Translational Opportunities.Gastroenterology · 2025Review
- Visium spatial transcriptomics and proteomics identifies novel hepatic cell populations and transcriptomic signatures of alcohol-associated hepatitis.Alcohol, clinical & experimental research · 2025Article
- Neutrophils insert elastase into hepatocytes to regulate calcium signaling in alcohol-associated hepatitis.The Journal of clinical investigation · 2024Article
- Role of immune cell interactions in alcohol-associated liver diseases.Liver research (Beijing, China) · 2024Review
- Article
- The Role of CCL24 in Primary Sclerosing Cholangitis: Bridging Patient Serum Proteomics to Preclinical Data.Cells · 2024Article
- Platelets in Alcohol-Associated Liver Disease: Interaction With Neutrophils.Cellular and molecular gastroenterology and hepatology · 2024Review
- Elucidating the role of 4-hydroxy-2(3H)-benzoxazolone in chronic alcoholic liver disease via transcriptomics and metabolomics.Frontiers in pharmacology · 2024Article
- Ductular reaction-associated neutrophils promote biliary epithelium proliferation in chronic liver disease.Journal of hepatology · 2023Article
- Intestinal Microbiotas and Alcoholic Hepatitis: Pathogenesis and Therapeutic Value.International journal of molecular sciences · 2023Review
- Mitochondrial Dysfunction: At the Nexus between Alcohol-Associated Immunometabolic Dysregulation and Tissue Injury.International journal of molecular sciences · 2023Review
- Cell-Specific Regulation of Inflammatory Cytokines and Acute-Phase Proteins by the Glucocorticoid Receptor.Mediators of inflammation · 2023Article
- Apolipoprotein A-IV Has Bi-Functional Actions in Alcoholic Hepatitis by Regulating Hepatocyte Injury and Immune Cell Infiltration.International journal of molecular sciences · 2022Article
- Immunobiology of the biliary tract system.Journal of hepatology · 2022Review
- Narrative Review: Glucocorticoids in Alcoholic Hepatitis-Benefits, Side Effects, and Mechanisms.Journal of xenobiotics · 2022Review
- The Integrated Analysis of Transcriptomics and Metabolomics Unveils the Therapeutical Effect of Asiatic Acid on Alcoholic Hepatitis in Rats.Inflammation · 2022Article
- Epigenetics of alcohol-related liver diseases.JHEP reports : innovation in hepatology · 2022Review
- Impaired regulation of PMCA activity by defective CFTR expression promotes epithelial cell damage in alcoholic pancreatitis and hepatitis.Cellular and molecular life sciences : CMLS · 2022Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 4 countries.
Funding
Abstract
BACKGROUND &
objectivesAlcoholic hepatitis (AH) is a common but life-threatening disease with limited treatment options. It is thought to result from hepatocellular damage, but the presence of cholestasis worsens prognosis, so we examined whether bile ducts participate in the pathogenesis of this disease.
designCholangiocytes derived from human bile ducts were co-cultured with neutrophils from patients with AH or controls. Loss of type 3 inositol 1,4,5-trisphosphate receptor (ITPR3), an apical intracellular calcium channel necessary for cholangiocyte secretion, was used to reflect cholestatic changes. Neutrophils in contact with bile ducts were quantified in liver biopsies from patients with AH and controls and correlated with clinical and pathological findings.
resultsLiver biopsies from patients with AH revealed neutrophils in contact with bile ducts, which correlated with biochemical and histological parameters of cholestasis. Cholangiocytes co-cultured with neutrophils lost ITPR3, and neutrophils from patients with AH were more potent than control neutrophils. Biochemical and histological findings were recapitulated in an AH animal model. Loss of ITPR3 was attenuated by neutrophils in which surface membrane proteins were removed. RNA-seq analysis implicated integrin β1 (ITGB1) in neutrophil-cholangiocyte interactions and interference with ITGB1 on cholangiocytes blocked the ability of neutrophils to reduce cholangiocyte ITPR3 expression. Cell adhesion molecules on neutrophils interacted with ITGB1 to trigger RAC1-induced JNK activation, causing a c-Jun-mediated decrease in ITPR3 in cholangiocytes.
conclusionsNeutrophils bind to ITGB1 on cholangiocytes to contribute to cholestasis in AH. This previously unrecognised role for cholangiocytes in this disease alters our understanding of its pathogenesis and identifies new therapeutic targets.
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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.