ArticleJournal of hepatology2018
Macrophages contribute to the pathogenesis of sclerosing cholangitis in mice.
Article in Journal of hepatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 177 citations in OpenAlex.
- Phase 2, open-label, rollover study of cenicriviroc for liver fibrosis associated with metabolic dysfunction-associated steatohepatitis.Hepatology communications · 2024Trial
- Improvement in Hepatic Fibrosis Biomarkers Associated With Chemokine Receptor Inactivation Through Mutation or Therapeutic Blockade.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Trial
- Macrophage signaling associates with fibrogenic program activation in periductal fibroblasts in pediatric primary sclerosing cholangitis.JCI insight · 2026Article
- Primary sclerosing cholangitis displays distinct colonic mucosa topography yet a shared mast cell state with ulcerative colitis.Nature communications · 2026Article
- Bile acid retention in efferocytic macrophages shapes their inflammatory status during cholangitis.The Journal of experimental medicine · 2026Article
- Multimodal transcriptomics identifies metallothionein as a novel pathway in primary sclerosing cholangitis.Hepatology (Baltimore, Md.) · 2026Article
- Unveiling a novel macrophage-driven mechanism for obeticholic acid-induced liver injury in cholestatic: targeting NLRP12Cell biology and toxicology · 2026Article
- Therapeutic potential of tetrahydroxylated bile acids in reducing liver injury: Insights from thePediatric investigation · 2026Article
- GPCRs as key regulators in wound healing.Frontiers in cell and developmental biology · 2026Review
- Unraveling the pleiotropic effects of CCR2-dependent signal transduction in fibrosis development.Theranostics · 2026Review
- The gene regulatory networks shaping macrophage plasticity and altered function in fibrosis.Frontiers in immunology · 2026Review
- Zonation, Zonation, Zonation: The Real Estate of the Liver.Annual review of pathology · 2026Review
- Multi-omics mapping of PSC genetic risk to a high TWAS-active JAML+ lipid-associated macrophage program: bridging single-cell heterogeneity, spatial fibrotic niches, and machine learning selection.Frontiers in cell and developmental biology · 2026Article
- Dynamic cholangiocyte responses in a murine model of reversible cholestasis: macrophage remodeling and NF-Y-mediated TGFβ1 expression.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Macrophages in Autoimmune Liver Diseases: From Immune Homeostasis to Precision-Targeted Therapy.Biomedicines · 2025Review
- Myeloid cells in chronic liver inflammation.Cellular & molecular immunology · 2025Review
- Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells.Cellular & molecular immunology · 2025Review
- Central role for cholangiocyte pathobiology in cholestatic liver diseases.Hepatology (Baltimore, Md.) · 2025Review
- Conjugated bile acid-driven CD14JHEP reports : innovation in hepatology · 2025Article
- Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsMacrophages contribute to liver disease, but their role in cholestatic liver injury, including primary sclerosing cholangitis (PSC), is unclear. We tested the hypothesis that macrophages contribute to the pathogenesis of, and are therapeutic targets for, PSC.
methodsImmune cell profile, hepatic macrophage number, localization and polarization, fibrosis, and serum markers of liver injury and cholestasis were measured in an acute (intrabiliary injection of the inhibitor of apoptosis antagonist BV6) and chronic (Mdr2
resultsWe found increased peribiliary pro-inflammatory (M1-like) and alternatively-activated (M2-like) monocyte-derived macrophages in PSC compared to normal livers. In both SC models, genetic profiling of liver immune cells identified a predominance of monocytes/macrophages; immunohistochemistry confirmed peribiliary monocyte-derived macrophage recruitment (M1>M2-polarized), which paralleled injury onset and was reversed upon resolution in acute SC mice. PSC, senescent and BV6-treated human cholangiocytes released monocyte chemoattractants (CCL2, IL-8) and macrophage-activating factors in vitro. Pharmacological inhibition of monocyte recruitment by CVC treatment or CCR2 genetic deletion attenuated macrophage accumulation, liver injury and fibrosis in acute SC.
conclusionsPeribiliary recruited macrophages are a feature of both PSC and acute and chronic murine SC models. Pharmacologic and genetic inhibition of peribiliary macrophage recruitment decreases liver injury and fibrosis in mouse SC. These observations suggest monocyte-derived macrophages contribute to the development of SC in mice and in PSC pathogenesis, and support their potential as a therapeutic target. LAY SUMMARY: Primary sclerosing cholangitis (PSC) is an inflammatory liver disease which often progresses to liver failure. The cause of the disease is unclear and therapeutic options are limited. Therefore, we explored the role of white blood cells termed macrophages in PSC given their frequent contribution to other human inflammatory diseases. Our results implicate macrophages in PSC and PSC-like diseases in mice. More importantly, we found that pharmacologic inhibition of macrophage recruitment to the liver reduces PSC-like liver injury in the mouse. These exciting observations highlight potential new strategies to treat PSC.
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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.