SFB 841: Liver Inflammation: Infection, Immune Regulation and Consequences

肝脏炎症可由多种诱因引起，是世界上最常见的医学疾病之一。由此导致的肝硬变是导致死亡的十大原因之一。肝癌是世界上最常见的炎症性癌症，目前仅次于肺癌，成为癌症死亡的主要原因。虽然接种乙肝疫苗降低了肝癌发病率，特别是在较发达的东南亚国家，但其他肝病，特别是非酒精性脂肪性肝病和非酒精性脂肪性肝炎(NASH)，正在世界范围内造成发病率和死亡率的上升，特别是在西方国家。由于肝脏是中枢代谢器官，即使在应激状态下保护和维持其功能也是至关重要的。肝脏的保护机制包括它独特的再生能力，以及我们在这项研究中越来越多地了解到的它下调自身炎症反应的能力。这些特征导致了整体的进化优势，但在特定情况下可能是有害的，如肝脏感染，由于局部免疫反应受抑而成为慢性感染。同样，再生和耐受能力也可能诱导和促进恶性转化和癌症进展。CRC 841的中心假设是，肝脏中的免疫调节机制决定了对肝脏的感染性和炎症性侮辱的结果，以及修复过程中恶性转化的风险。在更好地了解调控机制的基础上，我们希望能够进行特定的治疗操作。此外，了解肝脏炎症将进一步深入了解炎症在健康和疾病中的启动、消退和后果的一般机制。

Liver inflammation can be caused by various triggers and is one of the most common medical conditions in the world. Resultant liver cirrhosis is one of the ten leading causes of death. Liver cancer is the most common inflammation-induced cancer in the world, and is now second only to lung cancer as the leading cause of cancer death. While hepatitis B vaccination has enabled a reduction in liver cancer incidence in particular in more developed South East Asian countries, other liver diseases, in particular non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH), are causing an increasing incidence and mortality worldwide, particularly in Western countries. As the liver is the central metabolic organ, it is of vital importance to protect and maintain its function even when stressed. Protective mechanisms of the liver include its unique capacity to regenerate and, as we are increasingly learning in this research initiative, its ability to down-regulate inflammatory reactions within itself. These features result in an overall evolutionary advantage, but may be detrimental in specific situations such as infections of the liver, that become chronic due to a dampened local immune response. Likewise, the regenerative and tolerogenic capacity may also induce and promote malignant transformation and cancer progression.The central hypothesis of the CRC 841 is that immune regulatory mechanisms in the liver determine the outcome of infectious and inflammatory insults to the liver, as well as the risk of malignant transformation during repair. On the basis of a better understanding of the regulatory mechanisms, we want to enable specific therapeutic manipulations. In addition, understanding liver inflammation will provide further insight in general mechanisms of initiation, resolution and consequences of inflammation in health and disease.