Intrahepatic signals involved in the recruitment and differentiation of IL-17 secreting T cells and Regulatory T cells i

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Liver disease is increasing in Western countries and there are nowhere near enough organ donors to treat the number of patients with end-stage liver disease. Chronic hepatitis leads to scarring (cirrhosis) and liver failure and the only effective treatment is liver transplantation. Lymphocytes are a type of white blood cell and an important part of the body‘s immune system. They normally fight infections but if they persist or become inappropriately activated they can cause liver injury as part of chronic hepatitis or inflammation that leads to scarring and liver failure. Lymphocytes are directed to sites of liver inflammation by molecules called chemokines that are produced in response to inflammation. These chemokines are specific in that they can direct the entry/ recruitment of particular groups of lymphocytes to specific tissues. These groups include damaging effector lymphocytes and regulatory cells which damp down inflammation leading to resolution of damage. The outcome of liver injury depends on the balance between these inflammatory and anti-inflammatory regulatory lymphocytes which in turn will be determined by a) which types of cells are recruited to the liver from blood b) signals within the liver that shape the survival, activation and expansion of specific lymphocytes. Shifting the balance towards anti-inflammatory regulatory cells may prevent liver inflammation and promote resolution thereby reversing progression to fibrosis/cirrhosis. We would like to investigate the molecular signals involved and then exploit our knowledge to develop novel therapeutic approaches using anti-inflammatory regulatory lymphocytes as cell therapy to treat chronic liver diseases.