Animal models of autoimmune liver disease

Autoimmune liver diseases in humans are characterized by chronic active hepatitis with serum autoantibodies, hypergammaglobulinemia and liver pathology showing necroinflammatory disease and fibrosis. There are an increasing number of autoantigens believed to be associated with various autoimmune liver diseases. This review will briefly outline human autoimmune hepatitis and the immunology of the liver. Various murine models of liver inflammation will be discussed, including transgenic and non-transgenic models, with emphasis on how these models aid in our knowledge of the mechanisms of disease development and chronicity. There are limitations with all of the models, including a preponderance of T-cell-focused responses. Murine models do not easily develop fibrosis, a hallmark of autoimmune hepatitis in humans. Different experimental models may not reach the same conclusions with differences between immune responses. However, this multiplicity of responses does not necessarily imply that these models are inappropriate for the study of liver immunology and autoimmune liver diseases, as different autoantigens may induce different liver responses. Knowledge of how the liver differs from other immune organs is essential to further our understanding of liver-specific autoimmunity. The plethora of antigens implicated in autoimmune hepatitis in humans predicts that multiple mechanisms may play a role in precipitating disease in the susceptible individual.