Cellular senescence in the cholangiopathies: a driver of immunopathology and a novel therapeutic target

Christy E. Trussoni, Steven P. O’Hara, Nicholas F. LaRusso

Research output: Contribution to journalReview articlepeer-review

Abstract

The cholangiopathies are a group of liver diseases that affect cholangiocytes, the epithelial cells that line the bile ducts. Biliary atresia (BA), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are three cholangiopathies with significant immune-mediated pathogenesis where chronic inflammation and fibrosis lead to obliteration of bile ducts and eventual liver cirrhosis. Cellular senescence is a state of cell cycle arrest in which cells become resistant to apoptosis and profusely secrete a bioactive secretome. Recent evidence indicates that cholangiocyte senescence contributes to the pathogenesis of BA, PBC, and PSC. This review explores the role of cholangiocyte senescence in BA, PBC, and PSC, ascertains how cholangiocyte senescence may promote a senescence-associated immunopathology in these cholangiopathies, and provides the rationale for therapeutically targeting senescence as a treatment option for BA, PBC, and PSC.

Original languageEnglish (US)
JournalSeminars in Immunopathology
DOIs
StateAccepted/In press - 2022

Keywords

  • Biliary epithelial cell
  • Cellular senescence
  • Cholangiopathies
  • Immunosenescence
  • Senescence-associated secretory phenotype
  • Senolytics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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