Pathogenesis of autoimmune hepatitis: from break of tolerance to immune-mediated hepatocyte apoptosis.
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.
Lapierre
Pascal
P
Service de gastroentérologie, hépatologie et nutrition, Hôpital Sainte-Justine, Montréal, Québec, Canada.
Béland
Kathie
K
Alvarez
Fernando
F
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D019693:Hepatitis, Autoimmune / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D022781:Hepatocytes / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*