Completed Heart, Stroke & Blood Infection & Immunity

Determining how CD4+ T cells regulate adult liver stem cells during regeneration

In plain English

AI plain-English summary

The liver’s own repair system falters during chronic injury, and immune cells may hold the key to restarting it. When the liver is repeatedly damaged—by alcohol, fatty liver disease, or viral hepatitis—its usual method of healing, through hepatocyte division, fails. Instead, bile duct cells step in, transforming into new hepatocytes to patch the damage. But no one knows what controls this backup repair process. The researcher has observed immune cells clustering near bile ducts in diseased human livers, and early data suggest these cells can influence regeneration. This project will use human disease models to identify which immune cells are involved and how they signal to bile ducts. If the research succeeds, it could lead to drugs that coax the liver to heal itself without a transplant. Chronic liver disease is a growing global problem, and current treatments only slow its progression. Understanding this immune–bile duct conversation is fundamental science—it will not produce a therapy tomorrow. But similar discoveries about immune regulation have already reshaped cancer treatment and autoimmune disease management. A deeper grasp of how the body’s own cells and immune system cooperate during injury could eventually unlock regenerative therapies for millions.

View original technical description
The liver normally recovers after injury in most situations through the division of hepatocytes, but this is fundamentally impaired during chronic liver injury. During chronic liver injury, bile ducts in the liver react in response to liver damage. This process is important for liver regeneration as some cells of the bile ducts can become hepatocytes when the liver is severely injured. However, the factors that control this process remain unknown. Immune cells infiltrate the liver and are observed close to the bile cuts during chronic liver injury and my initial data suggest that these immune cells control can affect how the liver regenerate. In this project I will use multiple models of human liver disease to investigate what type of immune cells are involved and how they interact with bile ducts to control liver regeneration. This research will enable the design of new therapies to treat chronic liver diseases which is currently a major issue worldwide.

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Researchers

Wei-Yu Lu (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

Understanding the molecular mechanisms of adult liver regeneration.
The molecular basis of regulatory T cell recruitment to the inflamed liver
Investigation of the role of hepatic stellate cell alpha-v integrins during liver regeneration using a novel conditional genetic system.
Defining the functional role of the progenitor cell-laminin interaction during liver regeneration
The role of tumour necrosis factor superfamily receptors and the innate immune system in liver inflammation and epithelial to mesenchymal transition

Original classification

Fellowship

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