Innate immunity and primary biliary cirrhosis

Carlo Selmi, Ana Lleo, Simone Pasini, Massimo Zuin, M. Eric Gershwin

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

There has been a rapid growth in our understanding of the molecular bases of primary biliary cirrhosis (PBC). These efforts were initiated when the immunodominant mitochondrial autoantigen was cloned and sequenced. Using the recombinant cloned antigen as a tool, research has focused on the effector mechanisms of disease and the uniqueness of the primary target tissue, the intrahepatic bile ducts. Most recently, there have been experimental data suggesting that innate immunity changes may be critical to the initiation and perpetuation of the autoimmune injury, as in the case of the enhanced response of monocytes and memory B cells to infectious stimulation and environmental mimics. These observations are important as they help fill in the many gaps which remain on the most difficult subject of autoimmunity, etiology. Indeed, based on the available data, several experimental models of PBC have been developed. These models illustrate and suggest that PBC can be initiated by several mechanisms, all of which lead to loss of tolerance to the mitochondrial antigens. However, once this adaptive response develops, it appears that much of the subsequent pathology is exacerbated by innate responses. We suggest that future therapeutic efforts in PBC will depend heavily on understanding the nature of this innate immune responses and methodology to blunt their cytotoxicity.

Original languageEnglish (US)
Pages (from-to)45-51
Number of pages7
JournalCurrent Molecular Medicine
Volume9
Issue number1
DOIs
StatePublished - 2009

Fingerprint

Biliary Liver Cirrhosis
Innate Immunity
Antigens
Autoantigens
Pathology
Cytotoxicity
Ducts
Cells
Tissue
Intrahepatic Bile Ducts
Data storage equipment
Autoimmunity
Monocytes
B-Lymphocytes
Theoretical Models
Wounds and Injuries
Growth
Research
Therapeutics

Keywords

  • Apoptosis
  • Autoimmune cholangitis
  • Memory B cells
  • Monocyte
  • NK cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine

Cite this

Innate immunity and primary biliary cirrhosis. / Selmi, Carlo; Lleo, Ana; Pasini, Simone; Zuin, Massimo; Gershwin, M. Eric.

In: Current Molecular Medicine, Vol. 9, No. 1, 2009, p. 45-51.

Research output: Contribution to journalArticle

Selmi, Carlo ; Lleo, Ana ; Pasini, Simone ; Zuin, Massimo ; Gershwin, M. Eric. / Innate immunity and primary biliary cirrhosis. In: Current Molecular Medicine. 2009 ; Vol. 9, No. 1. pp. 45-51.
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