A role for hepatic sinusoidal endothelial cell antigen presentation in the generation of immune tolerance in hepatitis C

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170 million people worldwide are infected with the hepatitis C virus (HCV). A significant proportion of infected individuals develop liver scarring (cirrhosis) and liver cell cancer. To access the liver cells which the virus can infect it enters the liver via blood vessels in the liver called sinusoids. These are lined by specialised cells - hepatic sinusoidal endothelial cells (HSEC) - which express receptors that can bind HCV.In health these cells play an important role in scavenging food proteins and other molecules from the blood and can interact with cells of the immune system. The effect of this interaction is to prevent the immune system from destroying harmless food proteins by a process called immune tolerance. We hypothesise that HSEC are critical in HCV infection by 1) taking up the virus from blood and concentrating it in the liver and 2) inducing immune tolerance to the virus, preventing its effective clearance from infected liver cells.We will study HSEC from human tissue to determine how they interact with HCV and the immune system in HCV infection. Increased understanding of this critical aspect of the disease will allow us to develop new therapies to prevent chronic infection with HCV.