ArticleJCI insight2016
IRF5 governs liver macrophage activation that promotes hepatic fibrosis in mice and humans.
Article in JCI insight, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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.
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Who cites it
42 citing papers in PubMed, 61 citations in OpenAlex.
- Inhibition of IRF5 hyperactivation protects from lupus onset and severity.The Journal of clinical investigation · 2020Trial
- Decoding fibroblast activation: Transcriptional networks in hepatic stellate cells and across fibrotic organs (Review).International journal of molecular medicine · 2026Review
- Article
- Histone demethylase KDM7A negatively regulates fibrotic macrophage polarization and lung fibrosis progression.Communications biology · 2026Article
- Immune crosstalk in metabolic dysfunction-associated steatotic liver disease: interactions between innate and adaptive immunity.Frontiers in immunology · 2026Review
- Macrophage and inflammation in diabetes and metabolic dysfunction-associated steatotic liver disease: From mechanisms to therapeutic strategies.World journal of diabetes · 2025Review
- RNA Sequencing-Based Transcriptome Analysis of Liver in Laying Hens Supplemented with Dietary ProbioticVeterinary sciences · 2025Article
- The Intriguing Roles of Cytokines in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Narrative Review.Current obesity reports · 2025Review
- Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics.MedComm · 2025Review
- Aging and metabolic dysfunction-associated steatotic liver disease: a bidirectional relationship.Frontiers of medicine · 2025Review
- Disruption of the novel nested geneeLife · 2025Article
- Interferon regulatory factor 5: a potential target for therapeutic intervention in inflammatory diseases.Frontiers in immunology · 2025Review
- The Role of Interferon Regulatory Factors in Liver Diseases.International journal of molecular sciences · 2024Review
- Macrophage RAGE activation is proinflammatory in NASH.JCI insight · 2024Article
- Genetic variants of interferon-response factor 5 are associated with the incidence of chronic kidney disease: the D.E.S.I.R. study.Genes and immunity · 2023Article
- The bidirectional immune crosstalk in metabolic dysfunction-associated steatotic liver disease.Cell metabolism · 2023Review
- Comparative analyses of monocyte memory dynamics from mice to humans.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- An Integrative Multiomics Framework for Identification of Therapeutic Targets in Pulmonary Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The progress of autoimmune hepatitis research and future challenges.Open medicine (Warsaw, Poland) · 2023Review
- Macrophages and the development and progression of non-alcoholic fatty liver disease.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatic fibrosis arises from inflammation in the liver initiated by resident macrophage activation and massive leukocyte accumulation. Hepatic macrophages hold a central position in maintaining homeostasis in the liver and in the pathogenesis of acute and chronic liver injury linked to fibrogenesis. Interferon regulatory factor 5 (IRF5) has recently emerged as an important proinflammatory transcription factor involved in macrophage activation under acute and chronic inflammation. Here, we revealed that IRF5 is significantly induced in liver macrophages from human subjects developing liver fibrosis from nonalcoholic fatty liver disease or hepatitis C virus infection. Furthermore, IRF5 expression positively correlated with clinical markers of liver damage, such as plasma transaminase and bilirubin levels. Interestingly, mice lacking IRF5 in myeloid cells (MKO) were protected from hepatic fibrosis induced by metabolic or toxic stresses. Transcriptional reprogramming of macrophages lacking IRF5 was characterized by immunosuppressive and antiapoptotic properties. Consequently, IRF5 MKO mice respond to hepatocellular stress by promoting hepatocyte survival, leading to complete protection from hepatic fibrogenesis. Our findings reveal a regulatory network, governed by IRF5, that mediates hepatocyte death and liver fibrosis in mice and humans. Therefore, modulating IRF5 function may be an attractive approach to experimental therapeutics in fibroinflammatory liver disease.
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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.