Mouse Models for Experimental Autoimmune Hepatitis: Limits and Chances
Mouse Models for Experimental Autoimmune Hepatitis: Limits and Chances
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DOI：
10.1159/000282067
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发表时间：
2010-01-01
影响因子：
2.3
通讯作者：
Jaeckel, Elmar
中科院分区：
文献类型：
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作者：
Hardtke-Wolenski, Matthias;Jaeckel, Elmar
研究人类自身免疫性肝炎（AIH）的难点通常是诊断时间较晚，随后是长期的免疫抑制，以及人类免疫反应通常只能在外周血中进行研究。因此，确定AIH发病的动物模型，以及标准治疗干预措施的积极影响，是了解该疾病及其病理生理学的关键，并为新的治疗选择或更好的预防提供平台。一个多世纪以来，缺乏针对肝细胞的慢性免疫反应的可靠模型一直是AIH研究中的一个关键问题。最初试图打破对肝组织的耐受性导致轻度和短暂性肝炎。许多转基因模型显示了肝脏特异性免疫调节的不同方面。肝脏特异性T细胞的命运正处于激烈的研究之中，许多机制已经被证明是无知、能量、缺失或TCR下调。此外，这些研究明确了专业抗原呈递细胞，特别是肝窦细胞的作用。其他模型显示了肝脏中T细胞活化的机制以及适应性和先天免疫细胞的相互作用。最近，一些方法被用来建立类似人类疾病的慢性AIH模型。这些尝试可能为研究AIH的发病及其病理生理学开辟新的研究机会，并可能为治疗和预防研究提供新的选择。版权所有：S. Karger AG，巴塞尔
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. Copyright (C) 2010 S. Karger AG, Basel