Role of CXCR6/CXCL16 in steatohepatitis

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Liver disease is a significant health problem in the UK where rates of liver disease are rising as a consequence of hepatitis C infection, rising rates of alcoholic liver disease (ALD) and a high prevalence of non-alcoholic fatty liver disease (NALFD) a liver disease related to obesity, diabetes and high blood pressure. Despite their different causes most chronic liver diseases arise as a consequence of an inflammatory response to liver injury that causes scarring and destruction of the liver leading to liver failure. The inflammation in the liver is due to white blood cells leaving the bloodstream and entering liver tissue where they can orchestrate liver damage. This process is controlled by numerous molecules in the liver and on white cells that promote their entry and retention in the liver. We propose to focus our research on one of these molecules, a chemokine called CXCL16 and its corresponding receptor on white cells, CXCR6. We have already shown that CXCR6 is concentrated on white cells that cause liver damage and I will now determine precisely what this receptor does and by using recently developed specific inhibitors of CXCR6, elucidate the inflammatory process and investigate new means of treating it.