Lapierre Pascal, Béland Kathie, Alvarez Fernando
Service de gastroentérologie, hépatologie et nutrition, Hôpital Sainte-Justine, Montréal, Québec, Canada.
Transl Res. 2007 Mar;149(3):107-13. doi: 10.1016/j.trsl.2006.11.010.
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.
在分子水平上理解自身免疫性肝炎（AIH）的发病机制和进展对于开发新的预防和治疗策略可能至关重要。最近开发的小鼠模型已能够识别参与这种自身免疫性疾病发生和持续存在的各种机制。对这些模型的研究表明，针对肝脏表达抗原的外周耐受性破坏足以诱发自身免疫性肝病，且这种情况可在无先前肝脏损伤的情况下发生。最近的数据还表明，肝脏在免疫反应后选择性募集并诱导活化的CD8 + T细胞凋亡。这种T细胞捕获过程涉及特定趋化因子和黏附分子的表达，并且这些分子被认为在自身免疫性肝炎的起始和持续存在中起重要作用。由自身反应性T细胞诱导的肝细胞凋亡遵循特定途径，这些途径可能成为新治疗药物的靶点。针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（如原发性胆汁性肝硬化和移植物抗宿主病）的患者。
