Macrophage heterogeneity and plasticity in liver injury and repair mechanisms

Area of Science:

• Immunology
• Hepatology
• Cell Biology

Background:

• Hepatic macrophages, comprising embryonic Kupffer cells (emKCs) and monocyte-derived macrophages (MoMFs), are vital for maintaining liver homeostasis.
• These cells are implicated in the pathogenesis of liver diseases, notably metabolic dysfunction-associated steatotic liver disease (MASLD).
• Recent advances highlight their role in liver repair and regeneration through interactions with hepatocytes and hepatic stellate cells (HSCs).

Purpose of the Study:

• To review the complex roles of hepatic macrophages in liver injury and repair.
• To emphasize their involvement in steatosis, inflammation, fibrosis, and regeneration.
• To explore potential macrophage-targeted therapeutic strategies for liver diseases.

Main Methods:

• Review of current literature on hepatic macrophage biology.
• Integration of findings from single-cell and spatial omics technologies.
• Incorporation of insights from intravital microscopy studies.

Main Results:

• Hepatic macrophages exhibit significant phenotypic and spatial heterogeneity, with subsets like lipid-associated macrophages (LAMs) identified in disease regions.
• Macrophage subsets integrate systemic and local signals to modulate cellular responses in hepatocytes, HSCs, and other immune cells.
• Advanced imaging techniques reveal previously unknown functional properties within the liver's spatial context.

Conclusions:

• Hepatic macrophages are central regulators of liver injury, inflammation, fibrosis, and regeneration.
• Understanding macrophage heterogeneity and function is key to developing targeted therapies for liver diseases.
• Future research directions include leveraging omics and imaging data for novel therapeutic interventions.