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

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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.