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Nature Research, Nature, 7364(477), p. 335-339, 2011

DOI: 10.1038/nature10400

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

Journal article published in 2011 by Claudia Günther, Eva Martini, Nadine Wittkopf, Kerstin Amann, Benno Weigmann, Helmut Neumann, Maximilian J. Waldner, Stephen M. Hedrick, Stefan Tenzer ORCID, Markus F. Neurath, Christoph Becker
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Dysfunction of the intestinal epithelium is believed to result in excessive translocation of commensal bacteria into the bowel wall that drives chronic mucosal inflammation in Crohn's disease; an incurable inflammatory bowel disease in humans characterized by inflammation of the terminal ileum1. Beside the physical barrier established by the tight contact of cells, specialized epithelial cells such as Paneth cells and goblet cells provide innate immune defence functions by secreting mucus and antimicrobial peptides which hamper access and survival of bacteria adjacent to the epithelium2. Epithelial cell death is a hallmark of intestinal inflammation and has been discussed as a pathogenic mechanism driving Crohn's disease (CD) in humans3. However, the regulation of epithelial cell death and its role in intestinal homeostasis remains poorly understood.