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

Immune cells are directing the liver's own stem cells to repair damage during chronic disease, and researchers want to know exactly how they do it. The liver normally heals itself by having mature hepatocytes divide. But in chronic liver injury—caused by conditions like cirrhosis or hepatitis—that process fails. Instead, cells in the bile ducts step in, transforming into new hepatocytes. No one knows what controls this switch. This project will identify which immune cells cluster near bile ducts during injury and how they trigger the regeneration process. If the research succeeds, it could lead to drugs that boost the liver's natural repair capacity, reducing the need for transplants in the millions of people worldwide with chronic liver disease. The work is fundamental science—it will first map the cellular conversations between immune cells and bile-duct stem cells in human tissue models. Past discoveries in liver regeneration have already led to therapies for acute liver failure; this project targets the more common, slower-burning damage that currently has no cure.

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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