The immunophysiology and apoptosis of biliary epithelial cells: Primary biliary cirrhosis and primary sclerosing cholangitis

Kazuhito Kawata, Yoshimasa Kobayashi, M. Eric Gershwin, Christopher Bowlus

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Biliary epithelial cells (BECs) provide the first line of defense against lumenal microbes in the biliary system. BECs express a variety of pathogen recognition receptors and can activate several intracellular signaling cascades to initiate antimicrobial defenses, including production of several anti-microbial peptides, cytokines, chemokines, and adhesion molecules. BECs also secrete immunoglobulin A and interact with other cells through expression and release of adhesion molecules and immune mediators. Recently, several reports suggest a correlation between apoptosis and autoimmunity through ineffective clearance of self-antigens. Primary biliary cirrhosis (PBC) is a slowly progressive, autoimmune cholestatic liver disease characterized by highly specific antimitochondrial antibodies (AMAs) and the specific immune-mediated destruction of BECs. We have demonstrated that the AMA self-antigen, namely the E2 subunit of the pyruvate dehydrogenase complex, is detectable in its antigenically reactive form within apoptotic blebs from human intrahepatic biliary epithelial cells and activates innate immune responses. Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and the presence of concentric fibrosis of intrahepatic and/or extrahepatic bile ducts, eventually leading to cirrhosis. However, apoptosis does not appear to play a central role in PSC. Despite both diseases involving immune-mediated injury to bile ducts, apoptosis occurs more commonly overall in PBC where it likely plays a unique role.

Original languageEnglish (US)
Pages (from-to)230-241
Number of pages12
JournalClinical Reviews in Allergy and Immunology
Issue number3
StatePublished - Dec 2012


  • Apoptosis
  • Autoimmunity
  • Biliary epithelial cells
  • Primary biliary cirrhosis
  • Primary sclerosing cholangitis

ASJC Scopus subject areas

  • Immunology and Allergy


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