Chia-I Lin, Bi-Jhen Syu, Ya-Hui Chuang
Department of Clinical Laboratory Sciences and Medical Biotechnology, College of
Medicine, National Taiwan University, Taipei, Taiwan
Primary biliary cholangitis (PBC) is a progressive autoimmune liver disease characterized by immune-mediated destruction of intrahepatic small bile ducts, leading to decreased bile secretion, fibrosis, and eventual liver failure. Innate immunity plays a critical role in the natural history of PBC. IL-37, a member of the IL-1 family, is a fundamental inhibitor of innate inflammation. In this study, we used a xenobiotics (2-OA-OVA) immunization mouse model to investigate the role of inflammatory monocytes in PBC. In addition, we constructed and generated adeno-associated virus expressing human IL-37 (AAV-hIL-37) to investigate whether IL-37 could inhibit the inflammatory monocytes and alleviate PBC as a gene therapy. Our results showed that the inflammatory monocytes significantly increased at the early stage of 2-OA-OVA immunized PBC mice. However, there was no reduction in the liver inflammation and fibrosis in 2-OA-OVA immunized PBC mice intravenously injected with AAV-hIL-37 compared to mice injected with mock virus. Cell infiltration and inflammatory cytokine expressions in liver had no differences between AAV-mock and AAV-hIL-37 receiving PBC mice. Moreover, there were no differences in the numbers of inflammatory monocytes in the liver of PBC mice given AAV-hIL-37 compared to AAV-mock controls. In conclusion, inflammatory monocytes may play a role in the pathogenesis of PBC while AAV-hIL-37 neither inhibit inflammatory monocytes nor alleviate PBC features.