Apoptosis in immune-mediated liver diseases

Autoimmune diseases of the liver are chronic inflammatory processes leading to injury of hepatocytes and cholangiocytes. Cell death by apoptosis is a prominent feature in a variety of liver diseases. It is likely that apoptosis is the initial cellular response to liver and biliary injury and may thus initiate several cellular and cytokine cascades. Obviously, this cascade of events is of particular clinical importance. This short overview will focus on the role of apoptosis in immune-mediated liver diseases. Recently, also soluble forms of major histocompatibility complex class I-related chains A and closely related B (MIC A and B) were reported to be increased in the sera of patients with autoimmune and cholestatic liver diseases, and also in non-alcoholic steatohepatitis. MIC A and B are cell surface glycoproteins that function as indicators for cellular stress by displaying peptides derived from proteins degraded in the cytosol on the cell surface, and thus facilitate the recognition of intracellular antigens by circulating cytotoxic natural killer cells, leading to enhanced cell death. Nowadays rational-based strategies are being developed to suppress apoptotic cell death as a novel therapeutic option for the treatment of these liver diseases.