The liver neighbourhood watch: regulatory tissue-resident natural killer (NK) cells protect against liver decompensation in patients with chronic liver disease

Liver cirrhosis occurs when normal liver tissue is replaced by scar tissue, leading to the eventual failure of normal liver functions. Cirrhosis develops as a result of chronic liver disease, and it accounts for 170,000 deaths annually in Europe and more than 3,000 deaths annually in Ireland. Presently the only treatment is liver transplantation, however many patients die while waiting on a transplant. Better markers of disease progression and new therapeutic strategies to combat cirrhosis are urgently needed. This study will link three Dublin hospitals who currently care for patients with liver cirrhosis and will exploit new discoveries in liver immunology to identify immunological markers to predict the presence and rate of progression of liver cirrhosis. During the final stages of liver cirrhosis excessive inflammation occurs, which causes immune cells in the blood to stop functioning properly, however it is unclear whether this also affects immune cells resident within the liver itself. While previous studies have focused on the immune cells in the blood, the liver has its own specialised immune system and it is now clear that tissue-resident immune cells play an essential role in human health. We believe that liver-resident immune cells that normally control excessive immune activation are lost in cirrhotic patients. The goal of this study is to understand how liver-resident immune cells are affected during liver cirrhosis by looking at the changes in liver-resident immune cells in patients with liver cirrhosis who undergo liver transplantation. This research will identify key factors that regulate cirrhosis-causing-inflammation, which will provide new drug targets aimed at halting the progression of liver cirrhosis. This patient-orientated research will generate health knowledge needed to predict a patient's risk of liver failure and stop the progression of liver cirrhosis.

Award Date
04 July 2017
Award Value
€799,003
Principal Investigator
Dr Mark Robinson
Host Institution
Trinity College Dublin
Scheme
Emerging Investigator Awards