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Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis

Author

Listed:
  • Claudia Günther

    (Friedrich-Alexander-University, D-91054 Erlangen, Germany)

  • Eva Martini

    (Friedrich-Alexander-University, D-91054 Erlangen, Germany)

  • Nadine Wittkopf

    (Friedrich-Alexander-University, D-91054 Erlangen, Germany)

  • Kerstin Amann

    (Friedrich-Alexander-University, D-91054 Erlangen, Germany)

  • Benno Weigmann

    (Friedrich-Alexander-University, D-91054 Erlangen, Germany)

  • Helmut Neumann

    (Friedrich-Alexander-University, D-91054 Erlangen, Germany)

  • Maximilian J. Waldner

    (Friedrich-Alexander-University, D-91054 Erlangen, Germany)

  • Stephen M. Hedrick

    (University of California, San Diego, La Jolla, California 92093, USA)

  • Stefan Tenzer

    (Institute of Immunology, Johannes Gutenberg University, D-55131 Mainz, Germany)

  • Markus F. Neurath

    (Friedrich-Alexander-University, D-91054 Erlangen, Germany)

  • Christoph Becker

    (Friedrich-Alexander-University, D-91054 Erlangen, Germany)

Abstract

Epithelial cell death in intestinal inflammatory disease Two groups identify the regulation of death-receptor-induced necroptosis as an epithelial intrinsic mechanism that is important for the maintenance of immune homeostasis and the prevention of intestinal inflammation in mice. Welz et al. describe an unexpected physiological function for FADD (Fas-associated protein with death domain), an adaptor protein required for death-receptor-induced apoptosis. Mice with intestinal epithelial specific knockout of FADD develop severe colon inflammation due to increased death of FADD-deficient colonic epithelial cells. Günther et al. report a novel and unexpected function of caspase-8 in maintaining immune homeostasis in the gut. Caspase-8 expression by gut epithelial cells is shown to protect mice from TNF-mediated Paneth cell death and intestinal inflammation. Increased expression of the protein RIP3 was associated with the TNF-induced pathology, and elevated RIP3 expression was also found in intestinal Paneth cells of patients with Crohn's disease.

Suggested Citation

  • Claudia Günther & Eva Martini & Nadine Wittkopf & Kerstin Amann & Benno Weigmann & Helmut Neumann & Maximilian J. Waldner & Stephen M. Hedrick & Stefan Tenzer & Markus F. Neurath & Christoph Becker, 2011. "Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis," Nature, Nature, vol. 477(7364), pages 335-339, September.
    • Handle: RePEc:nat:nature:v:477:y:2011:i:7364:d:10.1038_nature10400
    DOI: 10.1038/nature10400
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    Cited by:

    1. Florian Beigel & Matthias Deml & Fabian Schnitzler & Simone Breiteneicher & Burkhard Göke & Thomas Ochsenkühn & Stephan Brand, 2014. "Rate and Predictors of Mucosal Healing in Patients with Inflammatory Bowel Disease Treated with Anti-TNF-Alpha Antibodies," PLOS ONE, Public Library of Science, vol. 9(6), pages 1-12, June.

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