Autoimmune Hepatitis and Stellate Cells: An Insight into the Role of Autophagy

Abstract

Autoimmune hepatitis is a necroinflammatory process of liver, featuring interface hepatitis by T cells, macrophages and plasma cells that invade to periportal parenchyma. In this process, a variety of cytokines are secreted and liver tissues undergo fibrogenesis, resulting in the apoptosis of hepatocytes. Autophagy is a complementary mechanism for restraining intracellular pathogens to which the innate immune system does not provide efficient endocytosis. Hepatocytes with their particular regenerative features are normally in a quiescent state, and, autophagy controls the accumulation of excess products, therefore the liver serves as a basic model for the study of autophagy. Impairment of autophagy in the liver causes the accumulation of damaged organelles, misfolded proteins and exceeded lipids in hepatocytes as seen in metabolic diseases. In this review, we introduce autoimmune hepatitis in association with autophagy signaling. We also discuss some genes and proteins of autophagy, their regulatory roles in the activation of hepatic stellate cells and the importance of lipophagy and tyrosine kinase in hepatic fibrogenesis. In order to provide a comprehensive overview of the regulatory role of autophagy in autoimmune hepatitis, the pathway analysis of autophagy in autoimmune hepatitis is also included in this article.

Rapamycin alleviates experimental autoimmune hepatitis by immunoregulation of Th1 and Th17 cells

“…Hepatic necrosis, apoptosis, ALT and AST had been proved to be signi cantly increased in autoimmune hepatitis, and had been demonstrated to be associated with disease severity [15,16]. We found rapamycin could signi cantly alleviate this pathological process.…”

Autophagy, Mitophagy and MicroRNA Expression in Chronic Hepatitis C and Autoimmune Hepatitis

“…The importance of autophagy has been emphasized in case of CHC, since it promotes HCV persistence and suppresses the activated immune response [15]. A possible link between autophagy and AIH has also been suggested [9], in which case however its role is not fully understood.…”

“…Stimulation of mTOR, a central issue in autoimmune disorders, also seems to contribute to inflammation in dysfunctional autophagy [37]. The fact that mTOR per se is an inhibitor of autophagy may explain the use of rapamycin as an mTOR inhibitor to treat AIH in the advanced stage [7,9].…”

“…Cell growth, development and homeostasis are the major processes in which autophagy is involved in order to maintain the balance between synthesis, degradation, and subsequent recycling of cellular products [7]. Several stress factors, including viral infection and autoimmunity, are known to activate autophagy [4,8,9]. Selective mitochondrial autophagy, termed mitophagy is particularly important in the elimination of mitochondrial dysfunction arising from aging and damage, thus, mitophagy plays crucial role in the reduction of oxidative stress and maintenance of cellular homeostasis [4,6,[10][11][12].…”

“…Autophagy is known to be involved in the activation of adaptive immunity, promoting the direct elimination of pathogens and simultaneous antigen processing and presentation to T cells [17]. Autophagy is therefore believed to be linked with the immune response seen in AIH, with involvement of several autophagy-related genes and various pathways via mechanisms that are still unresolved [9].…”