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

丙型肝炎病毒（HCV）是一种常见的传染性疾病，目前全球共有1.7亿人感染。相当一部分受感染的个体发展为肝瘢痕（肝硬化）和肝细胞癌。为了进入病毒可以感染的肝细胞，病毒通过肝脏中称为血窦的血管进入肝脏。肝窦内皮细胞（HSEC）表达能结合HCV的受体。在健康情况下，这些细胞在清除食物蛋白质和血液中的其他分子方面发挥重要作用，并能与免疫系统细胞相互作用。这种相互作用的效果是防止免疫系统通过称为免疫耐受的过程破坏无害的食物蛋白质。我们假设HSEC在HCV感染中起关键作用，1）从血液中摄取病毒并将其集中在肝脏中，2）诱导对病毒的免疫耐受，阻止其从感染的肝细胞中有效清除。我们将研究来自人体组织的HSEC，以确定它们如何与HCV和HCV感染中的免疫系统相互作用。增加对这种疾病的关键方面的了解将使我们能够开发新的治疗方法来预防HCV的慢性感染。

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.