Mouse models for experimental autoimmune hepatitis: limits and chances.
The difficulty in studying human autoimmune hepatitis (AIH) is usually the late time-point of diagnosis which is followed by long-standing immunosuppression and the fact that human immune responses can usually only be studied in peripheral blood. Therefore, animal models with defined onset of AIH and, ideally, a positive impact of standard therapeutic interventions are key to understanding the disease and its pathophysiology, and providing a platform for new therapy options or better prevention. For over a century, the lack of a reliable model with a chronic immune response against hepatocytes has been a key problem in AIH research. Initial attempts to break tolerance against liver tissue resulted in mild and transient hepatitis. Many transgenic models demonstrated different aspects of liver-specific immune regulation. The fate of liver-specific T cells is under intense research and many mechanisms have demonstrated ignorance, anergy, deletion or TCR downregulation. Furthermore, these studies defined a role of professional antigen-presenting cells and especially of liver sinusoidal cells. Other models have shown the mechanism of T cell activation in liver and the interaction of adaptive and innate immune cells. Most recently, some approaches have been made to establish models of chronic AIH resembling human disease. These attempts might open new research chances to study AIH onset and its pathophysiology, and they might result in new options for therapy and prevention research.
Hardtke-Wolenski
Matthias
M
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Jaeckel
Elmar
E
D000818:Animals; D004195:Disease Models, Animal; D019693:Hepatitis, Autoimmune / Q000276:immunology*; D007108:Immune Tolerance; D008099:Liver / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic