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Updated: Jun 7, 2025

Depletion and Reconstitution of Macrophages in Mice
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Understanding the complex macrophage landscape in MASLD.

Federico F De Ponti1,2, Zhuangzhuang Liu1,2, Charlotte L Scott1,2,3

  • 1Laboratory of Myeloid Cell Biology in Tissue Damage and Inflammation, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent 9052, Belgium.

JHEP Reports : Innovation in Hepatology
|November 11, 2024
PubMed
Summary

Hepatic macrophages, once thought uniform, are now known to be diverse in metabolic dysfunction-associated steatotic liver disease (MASLD). Understanding these diverse macrophage populations is key to developing new MASLD therapies.

Keywords:
Kupffer cellsLAMsMASHMASLDMacrophagesOsteopontinTREM2

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Area of Science:

  • Hepatology
  • Immunology
  • Cell Biology

Background:

  • Metabolic dysfunction-associated steatotic liver disease (MASLD) progresses from simple steatosis to severe outcomes like cirrhosis and cancer.
  • Macrophages are implicated in MASLD progression, but their exact roles remain unclear due to conflicting reports.
  • Previously, liver macrophages were considered a single type, but recent advances reveal significant heterogeneity.

Purpose of the Study:

  • To review current understanding of hepatic macrophage heterogeneity in MASLD.
  • To explore the distinct functions of various macrophage subsets in MASLD pathogenesis.
  • To identify knowledge gaps regarding macrophage roles in MASLD progression and potential therapeutic targeting.

Main Methods:

  • Summary of recent advancements in macrophage research.
  • Integration of findings from multi-parameter flow cytometry, single-cell RNA sequencing, and spatial proteogenomics.
  • Review of existing literature on hepatic macrophage populations in MASLD.

Main Results:

  • Hepatic macrophages are heterogeneous, comprising multiple subsets with distinct transcriptional profiles, even in healthy livers.
  • This heterogeneity is amplified in MASLD, with diverse resident and recruited macrophage populations.
  • Specific roles of these subsets in driving MASLD progression are still being elucidated.

Conclusions:

  • Deciphering the complexity of hepatic macrophage heterogeneity is crucial for understanding MASLD.
  • Targeting specific macrophage populations may offer a viable therapeutic strategy for MASLD.
  • Further research is needed to fully unravel the functions of distinct macrophage subsets in MASLD.