TY - JOUR
T1 - Cellular senescence in the cholangiopathies
T2 - a driver of immunopathology and a novel therapeutic target
AU - Trussoni, Christy E.
AU - O’Hara, Steven P.
AU - LaRusso, Nicholas F.
N1 - Funding Information:
This work was supported by National Institutes of Health Grant DK57993 (to N.F.L.), the Mayo Foundation, and the Mayo Clinic Center for Cell Signaling in Gastroenterology (P30DK084567) and PSC Partners Seeking a Cure Foundation (S.P.O.).
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2022/7
Y1 - 2022/7
N2 - 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.
AB - 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.
KW - Biliary epithelial cell
KW - Cellular senescence
KW - Cholangiopathies
KW - Immunosenescence
KW - Senescence-associated secretory phenotype
KW - Senolytics
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U2 - 10.1007/s00281-022-00909-9
DO - 10.1007/s00281-022-00909-9
M3 - Review article
C2 - 35178659
AN - SCOPUS:85124768663
SN - 1863-2297
VL - 44
SP - 527
EP - 544
JO - Seminars in Immunopathology
JF - Seminars in Immunopathology
IS - 4
ER -