Chronic intestinal inflammation in mice expressing viral Flip in epithelial cells

Ruder B, Murtadak V, Stürzl M, Wirtz S, Distler U, Tenzer S, Mahapatro M, Greten FR, Hu Y, Neurath M, Cesarman E, Ballon G, Günther C, Becker C (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Mucosal Immunology Nature Publishing Group: Open Access Hybrid Model Option A

Book Volume: 11

Pages Range: 1621-1629

Journal Issue: 6

DOI: 10.1038/s41385-018-0068-6

Abstract

Viruses are present in the intestinal microflora and are currently discussed as a potential causative mechanism for the development of inflammatory bowel disease. A number of viruses, such as Human Herpesvirus-8, express homologs to cellular FLIPs, which are major contributors for the regulation of epithelial cell death. In this study we analyzed the consequences of constitutive expression of HHV8-viral FLIP in intestinal epithelial cells (IECs) in mice. Surprisingly, expression of vFlip disrupts tissue homeostasis and induces severe intestinal inflammation. Moreover vFlipIEC-tg mice showed reduced Paneth cell numbers, associated with excessive necrotic cell death. On a molecular level vFlip expression altered classical and alternative NFκB activation. Blocking of alternative NFκB signaling by deletion of Ikka in vivo largely protected mice from inflammation and Paneth cell loss induced by vFLIP. Collectively, our data provide functional evidence that expression of a single viral protein in IECs can be sufficient to disrupt epithelial homeostasis and to initiate chronic intestinal inflammation.

Authors with CRIS profile

Vinay Murtadak Professur für Molekulare und Experimentelle Chirurgie Michael Stürzl Professur für Molekulare und Experimentelle Chirurgie Stefan Wirtz Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Markus Neurath Lehrstuhl für Innere Medizin I Claudia Günther Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Christoph Becker Professur für Molekulare Gastroenterologie

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

Johannes Gutenberg-Universität Mainz (JGU) DE Germany (DE) Northwell Health US United States (USA) (US) National Cancer Institute (NCI) US United States (USA) (US) Institut für Tumorbiologie und experimentelle Therapie / Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus DE Germany (DE) Weill Cornell Medicine US United States (USA) (US)

How to cite

APA:

Ruder, B., Murtadak, V., Stürzl, M., Wirtz, S., Distler, U., Tenzer, S.,... Becker, C. (2018). Chronic intestinal inflammation in mice expressing viral Flip in epithelial cells. Mucosal Immunology, 11(6), 1621-1629. https://doi.org/10.1038/s41385-018-0068-6

MLA:

Ruder, Barbara, et al. "Chronic intestinal inflammation in mice expressing viral Flip in epithelial cells." Mucosal Immunology 11.6 (2018): 1621-1629.

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