Pathogenesis of biliary tract injury in primary biliary cirrhosis

Hiromi Ishibashi, Shinji Shimoda

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Primary biliary cirrhosis (PBC) is histologically characterized by chronic nonsuppurative destructive cholangitis (CNSDC) associated with destruction of small bile ducts. The pathogenesis of PBC, predominance of female, or the reason why biliary duct is selectively involved, however, remains unknown. Infectious or non-infectious noxious insults such as xenobiotic chemicals may precipitate in the individual having a genetic background of PBC. Activation of innate immune response seems to be a key event in early PBC, leading to the autoimmune injury of small intrahepatic bile duct. Biliary epithelial cells possess an innate immune system consisting of the Toll-like receptor (TLR) family and recognize pathogen-associated molecular patterns (PAMPs). In PBC, dysregulated biliary innate immunity, namely hyper-responsiveness to PAMPs, is associated with the pathogenesis of cholangiopathy. Moreover, the targeted biliary epithelial cells (BEC) may play an active role in the perpetuation of autoimmunity by attracting immune cells via chemokine secretion. Biliary innate immune responses induce the production of two chemokines, CX3CL1 (fractalkine) and several Th1 shift chemokines, causing the migration of inflammatory cells including NK cells. TLR 4 ligand-stimulated NK cells destroy autologous BECs in the presence of interferon alpha (IFN-a) synthesized by TLR 3 ligand-stimulated monocytes. These findings give new insights in the pathogenesis of this mysterious disease, PBC.

Original languageEnglish
Pages (from-to)455-462
Number of pages8
JournalJapanese Journal of Clinical Immunology
Volume35
Issue number6
DOIs
Publication statusPublished - Jan 1 2012

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Biliary Liver Cirrhosis
Biliary Tract
Wounds and Injuries
Chemokine CX3CL1
Innate Immunity
Chemokines
Natural Killer Cells
Epithelial Cells
Toll-Like Receptor 3
Ligands
Intrahepatic Bile Ducts
Toll-Like Receptor 4
Toll-Like Receptors
Xenobiotics
Bile Ducts
Autoimmunity
Interferon-alpha
Cell Movement
Monocytes
Immune System

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Pathogenesis of biliary tract injury in primary biliary cirrhosis. / Ishibashi, Hiromi; Shimoda, Shinji.

In: Japanese Journal of Clinical Immunology, Vol. 35, No. 6, 01.01.2012, p. 455-462.

Research output: Contribution to journalArticle

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