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December 7, 2016JCI InsightOpen Access

IRF5 governs liver macrophage activation that promotes hepatic fibrosis in mice and humans

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Authors

FAFawaz AlzaïdFLFloriane LagadecMAMiguel Albuquerque

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Overview

Preclinical study demonstrates that macrophage IRF5 drives liver fibrosis in mice and human disease, highlighting IRF5 inhibition as a potential therapeutic target.

Key Points

  • To determine the role of interferon regulatory factor 5 (IRF5) in liver macrophage activation, hepatocyte survival, and the progression of hepatic fibrosis.
  • Assessed IRF5 expression in liver macrophages and analyzed correlations with liver damage markers (transaminases, bilirubin) in human subjects with NAFLD or hepatitis C virus.
  • Subjected myeloid-specific IRF5 knockout (MKO) mice and wild-type controls to metabolic or toxic liver injury models.
  • Evaluated transcriptional profiles, immunosuppressive signatures, and hepatocyte survival pathways in IRF5-deficient macrophages.
  • IRF5 expression was significantly induced in liver macrophages from patients with fibrotic liver disease and correlated positively with circulating transaminase and bilirubin levels.
  • Myeloid-specific deletion of IRF5 conferred complete protection against liver fibrosis induced by metabolic or toxic stress in mice.
  • IRF5 deficiency reprogrammed macrophages toward immunosuppressive and antiapoptotic phenotypes that promoted hepatocyte survival.

Cite This Study

Alzaïd et al. (2016) studied this question.

synapsesocial.com/papers/6aa135fa7ead44eb967775abhttps://doi.org/10.1172/jci.insight.88689
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1IRF5:RelA Interaction Targets Inflammatory Genes in Macrophages2014 · 129 citations
  2. 2Interferon regulatory factor 5 in myeloid cells promotes obstructive nephropathy-induced renal fibrosis in vivo2026
  3. 3IRF5 is required for iHPC differentiation in a mouse model of TLR7-driven macrophage activation syndrome and inhibition of IRF5 activity rescues from disease severity 36042025
  4. 4Non-transcriptional activity of IRF3 promotes liver fibrosis and stress granule assembly via a dsRNA-TLR3-dependent pathway in hepatic stellate cells2026
  5. 5IRF5 is required for inflammatory hemophagocyte differentiation and disease development in TLR7-mediated Macrophage Activation Syndrome 46432025