Immunological liver diseases // Drug Repurposing

Immunological liver diseases

Dr Patrick Bertolino and Dr David Bowen Liver Immnology Centenary InstituteThe Liver Immunology group aims to understand immune response within the liver and why these are biased towards the induction of tolerance. Understanding the mechanisms of intrahepatic immunity is critical for transplantation and infection by viruses that predominantly infect the liver such as Hepatitis B and C. Preventing immunity in the liver would improve the outcome of liver and other solid organ transplants.

The Liver Immunology Group is hoping to determine whether it is possible to influence the balance between tolerance and immunity in liver transplantation by influencing naïve T cell trafficking. Understanding these mechanisms would provide new strategies to enhance the survival of liver transplants and other solid organ transplants without immuno-suppression.

Latest Research

The research of our group is focused on the liver, an organ with unique tolerogenic properties. In many species, liver transplants are spontaneously accepted across a complete MHC mismatch and some viral infections, such as the one by the Hepatitis C virus, become chronic suggesting that the virus exploit this liver property to persist in the host.

The mechanisms involved in these processes remain unknown. The broad aims of our group are to understand the interactions between T lymphocytes and hepatic cells, the parameters that determine the balance between tolerance and immunity in the liver as well as those leading to chronic hepatitis.

Dr Patrick BertolinoWe are particularly interested in dissecting complex mechanisms of liver-induced tolerance of CD8+ T cells, which are responsible for graft rejection and virus clearance.

Our results have demonstrated that due to its unique architecture and slow blood flow the liver can retain and activate naïve CD8+ T cells, therefore acting as a site of primary activation. This finding contradicts the general accepted view that primary T cell responses can only be initiated in lymphoid tissues (lymph nodes and spleen). It is the first demonstration that a non-lymphoid organ can be the site of primary activation, a seminal finding with important implications for liver transplantation and Hepatitis C virus (HCV) research.

Group heads

Dr Patrick Bertolino

Group Head Liver Immunology

Dr PatrickBertolino received his PhD in 1992 from the University of Lyon in France. He then undertook two postdoctoral studies at the WEHI in Melbourne, Australia (1992-95) and ENS-Lyon in France (1995-97) before settling in at the Centenary Institute.

Dr Bertolino is internationally recognised as a world-leading expert in Liver Immunology and has made major contributions related the ability of the liver to induce tolerance in transplantation, and chronic HCV infection. He has demonstrated that naïve T cells can be activated directly in the liver. This fundamental finding overturned the
conventional belief that primary T-cell activation is unique to lymphoid tissues. His group investigates the consequences of these interactions to define the parameters that determine intrahepatic immunity/tolerance and chronic hepatitis. Dr.Bertolino has served on major scientific committees in Australia and is an NHMRC Senior Research Fellow since 2008.

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