Study of the origins and functions of distinct hepatic macrophage subsets in the pathogenesis of acute liver failure.

Paracetamol is a common household medication used to relieve pain. While it is safe and effective in therapeutic doses, when these doses are exceeded this can lead to acute liver failure as one of the breakdown products of paracetamol is toxic to the liver. This leads to the death of hepatocytes, the structural cells of the liver which in turn causes activation of the local immune system and local inflammation. This inflammation further contributes to liver failure. Paracetamol overdose is the most common cause of acute liver failure in the western world and is also one of the main causes for liver transplantation. Given the high risks and costs associated with liver transplantation and the lack of liver donors, further research is required to fully understand the immune response in order to be in a position to develop new therapies and prevent the need for liver transplantation. In this project, we will examine the functions of one type of immune cell, the macrophages, in acute liver failure. Although one of the oldest immune cells known to man, the study of these cells has been hampered by the lack of tools with which we can specifically study them. Having previously generated novel tools and techniques to study these cells, in this project we will utilise these tools
to better understand the functions of macrophages in acute liver failure.