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

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A Correction to this article was published on 31 March 2022

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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.

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Acknowledgements

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.).

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  1. Division of Gastroenterology and Hepatology and the Mayo Clinic Center for Cell Signaling in Gastroenterology, Mayo Clinic, Rochester, MN, USA

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

  2. Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street, SW, Rochester, MN, 55905, USA

    Nicholas F. LaRusso

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This article is a contribution to the special issue on: Tolerance and autoimmunity in the liver - Guest Editors: Christoph Schramm, Ansgar Lohse & Ye Oo

The original online version of this article was revised: Table 1 was incorrect. The corrected table 1 is given below.

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Trussoni, C.E., O’Hara, S.P. & LaRusso, N.F. Cellular senescence in the cholangiopathies: a driver of immunopathology and a novel therapeutic target. Semin Immunopathol 44, 527–544 (2022). https://doi.org/10.1007/s00281-022-00909-9

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