Immunological orchestration of liver fibrosis

Hajime Tanaka, Patrick S Leung, Tom P. Kenny, M. Eric Gershwin, Christopher Bowlus

Research output: Contribution to journalArticle

19 Scopus citations

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 antimitochondrial 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.

Original languageEnglish (US)
Pages (from-to)220-229
Number of pages10
JournalClinical Reviews in Allergy and Immunology
Volume43
Issue number3
DOIs
StatePublished - Dec 2012

Keywords

  • Fibrosis
  • Primary biliary cirrhosis
  • Xenobiotics

ASJC Scopus subject areas

  • Immunology and Allergy

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