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Updated: Jun 9, 2026
Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Targeting macrophages in liver fibrosis
Lydia González Del Barrio1,2,3, David H Ipsen3, Dominik R Pfister3
1Laboratory of Myeloid Cell Biology in Tissue Damage and Inflammation, VIB Center for Inflammation Research, VIB, Ghent, Belgium.
Abstract:
Fibrosis results from excessive deposition of extracellular matrix (ECM) components following tissue injury. While initially protective, chronic injury drives pathological ECM accumulation, tissue remodeling, and organ dysfunction. In the liver, fibrosis represents a common endpoint of chronic diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). Macrophages are central players of the fibrotic hepatic niche, modulating inflammatory signals, immune regulation, and tissue repair. Recent advances demonstrate that hepatic macrophages form a heterogeneous and highly dynamic compartment, adopting diverse activation states that extend far beyond the classical M1/M2 paradigm. Importantly, liver fibrosis is now recognized as a potentially reversible process, with resolution being closely linked to the reprogramming of macrophages towards restorative phenotypes characterized by enhanced efferocytosis, reduced pro-inflammatory signaling, and increased matrix degradation capacity. As a result, efforts to design macrophage-based therapeutic strategies are shifting from non-specific approaches such as inhibition of monocyte recruitment towards approaches that actively promote pro-resolution programs, including targeted in situ reprogramming and more recently cell-based macrophage therapies. In this review, we summarize the hepatic macrophage landscape in the fibrotic liver and discuss current opportunities and challenges in developing macrophage-based anti-fibrotic therapies.
Insights
Liver fibrosis, driven by excessive matrix buildup, involves dynamic macrophages. Therapeutic strategies now focus on reprogramming these macrophages towards restorative functions to reverse liver damage.
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.
