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The liver is an essential organ that aids in digestion, detoxification, and metabolism, among other critical processes. The liver’s ability to regenerate itself after injury is remarkable. However, the mechanism by which the liver can regenerate itself is still poorly known.
In order for the liver to regenerate, necrotic lesions and other damaged tissue must be removed. Recently, Feng et al. demonstrated the importance of monocyte-derived macrophages (MoMFs) in this process, and their findings were published in the Journal of Clinical Investigation. MoMFs are a group of the white blood cell family that specializes in responding to liver damage. After arriving in the liver, MoMFs consume dead cells and other debris. They also produce substances that aid in the liver’s natural repair mechanisms.
The study’s authors discovered that MoMFs continue to change as they seek to remove necrotic lesions. MoMFs promote inflammation during the initial phases of liver regeneration. In other words, they secrete chemicals that eliminate bacteria and other pathogens. MoMFs are pro-inflammatory early in liver regeneration but turn anti-inflammatory late in the process. This means that they produce compounds that help the liver heal and repair itself.
The team also discovered that MoMFs collaborate with other liver cells to clear away necrotic lesions. Hepatocytes (liver cells) are one type of cell that MoMFs interact with to promote regeneration. Additionally, MoMFs communicate with stellate cells (collagen-producing liver cells) to facilitate scar formation around the necrotic lesion.
Necrosis recovery was also observed in other models of liver injury studied by the scientists, including Klebsiella pneumoniae infection and ischemia/reperfusion. However, in models of hepatotoxin/drug-induced liver injury, such as those caused by carbon tetrachloride and acetaminophen, a distinct mechanism is presumably at work.
This investigation adds to the growing body of evidence that immunotherapies based on macrophages that specifically target hepatic necrosis may represent an effective new approach to treating a wide range of liver illnesses. Liver fibrosis, for instance, is a target for research into autologous macrophage treatment.
Macrophage-based immunotherapy methods for the treatment of hepatic necrosis need to be tested in clinical studies to determine if they are safe and effective. The study’s findings, however, lay a solid groundwork for creating such novel therapeutics.
Sources:
Dechun Feng et al. (2023). Monocyte-derived macrophages orchestrate multiple cell-type interactions to repair necrotic liver lesions in disease models, Journal of Clinical Investigation. DOI: 10.1172/JCI166954
https://phys.org/news/2023-09-monocyte-derived-macrophages-central-liver-regeneration.html
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Keywords: liver regeneration, macrophages, hepatocyte
