Targeting macrophages in liver fibrosis

Area of Science:

• Immunology
• Hepatology
• Pathology

Background:

• Fibrosis involves excessive extracellular matrix (ECM) deposition after chronic tissue injury, leading to organ dysfunction.
• In the liver, fibrosis is a common outcome of chronic diseases like metabolic dysfunction-associated steatotic liver disease (MASLD).
• Hepatic macrophages are key regulators of inflammation, immune responses, and tissue repair within the fibrotic liver microenvironment.

Purpose of the Study:

• To review the diverse roles of hepatic macrophages in liver fibrosis.
• To explore emerging therapeutic strategies targeting macrophages for liver fibrosis reversal.
• To discuss the challenges and opportunities in developing macrophage-based anti-fibrotic therapies.

Main Methods:

• Review of current literature on hepatic macrophage biology in fibrosis.
• Analysis of macrophage heterogeneity and dynamic activation states beyond the M1/M2 paradigm.
• Examination of therapeutic approaches including in situ reprogramming and cell-based therapies.

Main Results:

• Hepatic macrophages exhibit complex, dynamic phenotypes in fibrosis, extending beyond classical classifications.
• Liver fibrosis resolution is associated with macrophage reprogramming towards restorative functions (e.g., efferocytosis, matrix degradation).
• Therapeutic strategies are evolving from inhibiting monocyte recruitment to actively promoting pro-resolution macrophage programs.

Conclusions:

• Understanding the multifaceted hepatic macrophage landscape is crucial for developing effective anti-fibrotic therapies.
• Targeting macrophage reprogramming offers promising avenues for potentially reversing liver fibrosis.
• Further research is needed to optimize cell-based and in situ reprogramming strategies for clinical application.