Yüksel Muhammed, Laukens Debby, Heindryckx Femke, Van Vlierberghe Hans, Geerts Anja, Wong F Susan, Wen Li, Colle Isabelle
Department of Hepatology and Gastroenterology, Ghent University, Ghent, Belgium; Department of Endocrinology, Yale School of Medicine, New Haven, CT, USA.
Int J Exp Pathol. 2014 Oct;95(5):309-20. doi: 10.1111/iep.12090. Epub 2014 Aug 12.
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease associated with interface hepatitis, raised plasma liver enzymes, the presence of autoantibodies and regulatory T-cell (Tregs) dysfunction. The clinical course is heterogeneous, manifested by a fulminant or indolent course. Although genetic predisposition is well accepted, the combination with currently undefined environmental factors is crucial for the development of the disease. Progress in the development of reliable animal models provides added understanding of the pathophysiology of AIH, and these will be very useful in evaluating potential therapeutics. It appears that artificially breaking tolerance in the liver is easy. However, maintaining this state of tolerance breakdown, to get chronic hepatitis, is difficult because liver immune homeostasis is strongly regulated by several immune response inhibitory mechanisms. For example, Tregs are crucial regulators in acute and chronic hepatitis, and C57BL/6 mice are most prone to experimental AIH. Immunization of C57BL/6 mice with liver (AIH) autoantigens (CYP2D6/FTCD or IL-4R) and the disturbance of liver regulatory mechanism(s), leading to experimental AIH, are likely to be most representative of human AIH pathology.
自身免疫性肝炎（AIH）是一种慢性炎症性肝病，与界面性肝炎、血浆肝酶升高、自身抗体的存在以及调节性T细胞（Tregs）功能障碍相关。其临床病程具有异质性，表现为暴发性或隐匿性病程。尽管遗传易感性已被广泛认可，但与目前尚不明确的环境因素相结合对于该疾病的发生发展至关重要。可靠动物模型研发方面的进展增进了对AIH病理生理学的理解，这些模型在评估潜在治疗方法时将非常有用。似乎在肝脏中人为打破耐受性很容易。然而，要维持这种耐受性破坏状态以引发慢性肝炎却很困难，因为肝脏免疫稳态受到多种免疫反应抑制机制的强烈调控。例如，Tregs是急性和慢性肝炎中的关键调节因子，C57BL/6小鼠最易发生实验性AIH。用肝脏（AIH）自身抗原（CYP2D6/FTCD或IL-4R）免疫C57BL/6小鼠以及干扰肝脏调节机制从而导致实验性AIH，可能最能代表人类AIH的病理情况。
