Role of CXCR6/CXCL16 in steatohepatitis

在英国，肝病是一个严重的健康问题，由于丙型肝炎感染、酒精性肝病(ALD)和非酒精性脂肪性肝病(NALFD)的高发病率，肝病发病率正在上升。非酒精性脂肪性肝病是一种与肥胖、糖尿病和高血压相关的肝脏疾病。尽管原因不同，但大多数慢性肝病都是由于对肝脏损伤的炎症反应而产生的，这种炎症反应会导致肝脏形成疤痕和破坏，从而导致肝功能衰竭。肝脏的炎症是由于白细胞离开血流进入肝组织，在那里它们可以协调肝脏损伤。这个过程由肝脏和白细胞上的许多分子控制，这些分子促进它们进入和滞留在肝脏中。我们建议将研究重点放在其中一个分子上，即一种名为CXCL16的趋化因子及其相应的白细胞受体CXCR6上。我们已经证明CXCR6集中在导致肝脏损伤的白细胞上，我现在将准确地确定这种受体的作用，并通过使用最近开发的CXCR6的特定抑制剂，阐明炎症过程并探索治疗它的新方法。

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.