Pathogenesis of autoimmune hepatitis:: from break of tolerance to immune-mediated hepatocyte apoptosis
Pathogenesis of autoimmune hepatitis:: from break of tolerance to immune-mediated hepatocyte apoptosis
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DOI：
10.1016/j.trsl.2006.11.010
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发表时间：
2007-03-01
影响因子：
7.8
通讯作者：
Alvarez, Fernando
中科院分区：
文献类型：
--
作者：
Lapierre, Pascal;Beland, Kathie;Alvarez, Fernando
在分子水平上了解自身免疫性肝炎（AIH）的发病机制和进展，对于开发新的预防和治疗策略至关重要。最近开发的小鼠模型已经能够鉴定参与这种自身免疫性疾病的发展和持续的各种机制。对这些模型的研究表明，对肝脏表达抗原的外周耐受性破坏足以诱导自身免疫性肝病，其可以在没有先前肝损伤的情况下发生。最近的数据还表明，肝脏在免疫应答后选择性地募集并诱导活化的CD8+ T细胞的凋亡。这种T细胞捕获过程涉及特异性趋化因子和粘附分子的表达，这些分子被认为在自身免疫性肝炎的发生和持续中起重要作用。由自身反应性T细胞诱导的肝细胞凋亡遵循可被新治疗剂靶向的特定途径。对肝脏抗原免疫耐受性破坏的基础研究将有利于自身免疫性肝炎患者，以及患有其他慢性炎症性肝病的患者，如原发性胆汁性肝硬化和移植物抗宿主病。
Understanding the pathogenesis and progression of autoimmune hepatitis (AIH) at the molecular level could prove essential in developing new preventive and therapeutic strategies. Recently developed murine models have enabled the identification of various mechanisms involved in the development and perpetuation of this autoimmune disorder. Studies on these models have shown that a peripheral break of tolerance against liver-expressed antigens is sufficient to induce an autoimmune liver disease, which can occur without prior liver damage. Recent data have also shown that the liver selectively recruits and induces the apoptosis of activated CD8+ T cells after an immune response. This process of T-cell trapping involves the expression of specific chemokines and adhesion molecules, and these molecules are believed to play an important role in the initiation and perpetuation of autoimmune hepatitis. Hepatocyte apoptosis, induced by autoreactive T cells, follows specific pathways that could be targeted by new therapeutic agents. Basic research on the break of immune tolerance against liver antigens would be beneficial for patients with autoimmune hepatitis, as well as those suffering from other chronic inflammatory liver diseases, such as primary biliary cirrhosis and graft-versus- host diseases.