Our Liver Immunology program is studying the unique relationship between the liver and the immune system. Livers dampen down immunity to such an extent that they can be transplanted without rejection in some cases. Livers may not only be tolerated, but may also prevent the rejection of other organ grafts from the same donor, a process known as immune tolerance.
Our research is helping to improve our understanding of the liver and its impact on immune responses, both wanted and unwanted.
Although the liver’s tolerance effect leads to better outcomes in transplantation, it can be detrimental during infections such as hepatitis B, hepatitis C and malaria. These diseases can use the liver as a means of persisting, which can often lead to chronic infection.
Our Liver Immunology team is also providing some important clues to improve the success of human gene therapy. Having already shown that the liver, like the lymph nodes, can activate T cells, a key cell of the immune system, we are now investigating how the liver induces immune tolerance and how immunity can be enhanced in this organ.
Finding a Cure
The ultimate goal of our research is to improve treatments in organ transplantation, as well as deliver effective prevention and treatment of chronic liver disease.
Liver diseases caused by viral hepatitis represent an increasing health burden to the community. Hepatitis C (HCV) infection leads to cirrhosis and liver cancer, the third-leading cause of cancer-related death worldwide.
200,000 Australians are currently infected with HCV, with around 20,000 being diagnosed each year.
Our Liver Immunology researchers are gaining important insights in the relationship between the liver and the immune system, which will help improve treatments and patient outcomes in organ transplants and chronic liver disease.
The Liver Immunology Group uses unique transgenic mouse models, advanced imaging technology, and flow cytometry to dissect mechanisms regulating the balance between tolerance and immunity in the liver, and how T cells interact with and are instructed by hepatic cells in both healthy and diseased or transplanted liver. This research is important in transplantation, malaria and chronic hepatitis B and C virus (HBV and HCV) infections.
We focus on two current outstanding questions in Liver Immunology:
1) What are the mechanisms by which the liver induces tolerance to avoid acute injury? The liver is known to induce antigen-specific tolerance but mechanisms remain unknown. The group has shown that the hepatic microvasculature allows the liver to act as a site of primary T cell activation, a property previously thought to be restricted to secondary lymphoid tissues including the lymph nodes and the spleen. In contrast to activation in lymphoid tissues, intrahepatic activation leads to tolerance. The group has recently demonstrated that most liver-activated T cells invade hepatocytes and are rapidly destroyed in lysosomes.
2) What are the parameters allowing acute immune-mediated liver injury to become chronic? The liver is a site of many chronic infections but the parameters allowing progression to chronic hepatitis are unclear. The group has developed unique models of acute immune mediated hepatitis to dissect mechanisms leading to chronic hepatitis.
Patrick Bertolino, Head of Program
Phone: (02) 9565 6186
Patrick Bertolino leads the Liver Immunology Group and has been a Faculty member at the Centenary Institute since 2011. He is considered one of the leading experts in Liver Immunology internationally, and is acknowledged as the leader in this field in Australia, where he drives the main group working in this new and expanding discipline.
Patrick Bertolino has worked in the same field for the last 20 years in excellent research institutes, and has been trained by first class immunologists (ENS-Lyon, France: Chantal Rabourdin-Combe; WEHI: Jacques Miller; Centenary Institute: Barbara Fazekas de St Groth). During this time, he has developed unique transgenic mouse models and has acquired a leading international reputation in liver immunology. This reputation derives from original landmark pioneering papers that have transformed the field, and are now part of current paradigms. These include the first demonstration of naïve CD8 T cell activation in the liver, the first evidence of direct interaction between circulating T cells and hepatocytes, the role of intrahepatic T cell activation in tolerance, and the discovery that liver-activated T cells are deleted in the lysosomes of hepatocyte.
Patrick Bertolino has had consistent success in obtaining major international and national project grants as CIA, demonstrating independence and leadership. He has held continuous NHMRC funding since 2000: 2 Program Grants (PI 2005-9, CI 2010-4), and 6 Project grants (5 CIA, 1 CIB). He has also obtained highly competitive international funding (Roche Solid Organ Transplantation Research Foundation).