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Full NameDr Mark Robinson
Department:Department of Immunology
Organisation:Trinity College Dublin
- infectious disease and the immune system
- Infectious diseases
Liver cirrhosis accounts for 170,000 deaths per year in Europe, and once refractory complications arise in patients with cirrhosis, liver transplantation is currently the sole treatment option available. Utilising diseased liver tissue obtained during transplantation, peripheral blood samples, and liver biopsy sections, we are defining the changes in tissue-resident immune cells in disease. These data will inform the development of 3D hepatocyte cell culture systems to study the interactions of hepatocytes with resident immune cells, and the roles these interactions play in liver pathology. Finally, novel inflammatory biomarkers will be identified and tested in patients living with stable cirrhosis who are at risk of disease progression. This research into the clinical impact of dysfunction or loss of tissue-resident immune cell populations will shed new insights into liver cirrhosis and liver immunology. This will open up new avenues in our approach to the clinical management of liver cirrhosis, providing more options to patients living with chronic liver disease.
More information: https://www.tcd.ie/ttmi/
Liver cirrhosis is the end-stage of a range of different chronic liver diseases including viral hepatitis, fatty liver disease, and alcoholic liver disease. The clinical management of patients with liver cirrhosis is limited by the lack of prognostic markers that predict disease progression and the lack of therapeutics that block the progression of liver cirrhosis. Definition of the biological mechanisms that contribute to the progression of liver cirrhosis will provide novel prognostic markers and therapeutic agents. While previous studies have described systemic inflammation in peripheral blood samples from cirrhotic patients, it is unclear how this inflammation affects tissue-resident immune cells present within the liver and how this results in deteriorating liver function. We have recently described an abundant population of liver-resident natural killer (NK) cells in humans which are functionally distinct from peripheral blood NK cells. Preliminary evidence suggests this population of liver-resident NK cells plays an important immune regulatory role. In this study, we aim to:
1. Define the functional abilities of liver-resident CD56bright NK cells isolated from healthy donor livers and diseased explant livers obtained during transplantation from patients with liver cirrhosis
2. Determine whether hepatic tissue-resident immune cells alter the sensitivity of hepatocytes to inflammation -induced cell death during cirrhosis using ex vivo co-culture of liver immune cells and hepatocytes
3. Assess the prognostic value of novel immune biomarkers to predict the risk of decompensation in compensated cirrhotic patients