The liver is our largest internal organ that acts as a central hub for many physiological processes. Accordingly, immune responses within the liver are tightly controlled to prevent unnecessary organ damage. Although the liver has an unrivalled ability to regenerate when injured, persistent injury or inflammation can lead to the build-up of scar tissue as it attempts to repair. The build-up of such scar tissue (largely made up of extracellular matrix proteins) can results in liver dysfunction and the development of fibrosis/cirrhosis. But why do we care? Since 2018, liver fibrosis (and associated chronic liver disease) features in the top ten causes of premature death in the UK and kills individuals ~19 years younger than cancer or heart disease.

The liver is home to a number of 'residents', that provide specialised immune-surveillance and protection. We recently described a population of long-lived, tissue-resident T cells that are equipped with the necessary armoury to control hepatotropic infections, and showed that they can adapt phenotypically and functionally depending on cues from their microenvironment.

In addition, the liver has a unique population of stromal cells, that when exposed to chronic injury become the master regulators of fibrosis. It is these overactivated stromal cells that differentiate into myofibroblasts that then produce excessive amounts of extracellular matrix proteins, causing the liver to increase in stiffness and functionality to ultimately deteriorate.

Here in the Pallett lab we are interested in understanding how tissue-resident T cells and the underlying stromal cells ‘co-operate and communicate’ in the setting of fibrosis. We are particularly focussing on how these ‘local intrahepatic cells’ interact in both the healthy and diseased human liver, asking questions such as “can tissue-resident T cell contribute to tissue damage and/or tissue repair?” and “whether we can we harness the pathways involved to develop improved treatments for patients?”.