Clinical Reviews in Allergy & Immunology

, Volume 43, Issue 3, pp 220–229

Immunological Orchestration of Liver Fibrosis

  • Hajime Tanaka
  • Patrick S. C. Leung
  • Tom P. Kenny
  • M. Eric Gershwin
  • Christopher L. Bowlus
Article

DOI: 10.1007/s12016-012-8323-1

Cite this article as:
Tanaka, H., Leung, P.S.C., Kenny, T.P. et al. Clinic Rev Allerg Immunol (2012) 43: 220. doi:10.1007/s12016-012-8323-1

Abstract

Fibrosis represents the main pathophysiological consequence of all chronic inflammatory liver diseases and ultimately leads to the life-threatening clinical consequences of cirrhosis. Regardless of the underlying etiology, fibrosis involves interplay between cells of the immune systems and the direct mediators of fibrosis, including hepatic stellate cells. However, the precise physiological mechanism of liver fibrosis remains largely on enigma. Primary biliary cirrhosis (PBC) is a unique chronic, fibrosing liver disease affecting predominantly women and characterized by an immune-mediated specific destruction of the small intrahepatic bile ducts. The presence of highly specific anti-mitochondrial autoantibodies (AMA) as well as T cell responses directed agonist the pyruvate dehydrogenase E2 complex (PDC-E2) provides a unique opportunity to assess the interaction between specific immune responses and fibrogenesis. In addition, mouse models of PBC have been developed allowing the dissection of mechanisms involved in breakdown of immune tolerance, bile duct injury, and fibrosis. Recently, we reported that liver fibrosis could be induced in a xenobiotic-induced murine model of PBC by polyinosinic–polycytidylic acid (poly I:C) treatment as well as with the administration of α-galactosylceramide (α-GalCer). The aim of this article is to provide a current perspective of the immunological mechanisms that are significant in the fibrogenic processes, and potentially, for its regression by comparing PBC with other chronic inflammatory liver diseases.

Keywords

Primary biliary cirrhosis Fibrosis Xenobiotics 

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Hajime Tanaka
    • 1
  • Patrick S. C. Leung
    • 1
  • Tom P. Kenny
    • 1
  • M. Eric Gershwin
    • 1
  • Christopher L. Bowlus
    • 2
    • 3
  1. 1.Division of Rheumatology, Allergy and Clinical Immunology, School of MedicineUniversity of CaliforniaDavisUSA
  2. 2.Division of Gastroenterology and Hepatology, School of MedicineUniversity of CaliforniaDavisUSA
  3. 3.Division of Gastroenterology and HepatologyUniversity of CaliforniaSacramentoUSA

Personalised recommendations