Universität zu Köln

Vlantis, Katerina, Wullaert, Andy ORCID: 0000-0001-5012-654X, Polykratis, Apostolos ORCID: 0000-0001-6720-3302, Kondylis, Vangelis ORCID: 0000-0002-6970-8731, Dannappel, Marius, Schwarzer, Robin, Welz, Patrick, Corona, Teresa, Walczak, Henning ORCID: 0000-0002-6312-4591, Weih, Falk, Klein, Ulf, Kelliher, Michelle and Pasparakis, Manolis ORCID: 0000-0002-9870-0966 (2016). NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-kappa B-Dependent and -Independent Functions. Immunity, 44 (3). S. 553 - 568. CAMBRIDGE: CELL PRESS. ISSN 1097-4180

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Abstract

Intestinal epithelial cells (IECs) regulate gut immune homeostasis, and impaired epithelial responses are implicated in the pathogenesis of inflammatory bowel diseases (IBD). IEC-specific ablation of nuclear factor kappa B (NF-kappa B) essential modulator (NEMO) caused Paneth cell apoptosis and impaired antimicrobial factor expression in the ileum, as well as colonocyte apoptosis and microbiota-driven chronic inflammation in the colon. Combined RelA, c-Rel, and RelB deficiency in IECs caused Paneth cell apoptosis but not colitis, suggesting that NEMO prevents colon inflammation by NF-kappa B-independent functions. Inhibition of receptor-interacting protein kinase 1 (RIPK1) kinase activity or combined deficiency of Fas-associated via death domain protein (FADD) and RIPK3 prevented epithelial cell death, Paneth cell loss, and colitis development in mice with epithelial NEMO deficiency. Therefore, NEMO prevents intestinal inflammation by inhibiting RIPK1 kinase activity-mediated IEC death, suggesting that RIPK1 inhibitors could be effective in the treatment of colitis in patients with NEMO mutations and possibly in IBD.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Vlantis, Katerina UNSPECIFIED UNSPECIFIED UNSPECIFIED Wullaert, Andy UNSPECIFIED orcid.org/0000-0001-5012-654X UNSPECIFIED Polykratis, Apostolos UNSPECIFIED orcid.org/0000-0001-6720-3302 UNSPECIFIED Kondylis, Vangelis UNSPECIFIED orcid.org/0000-0002-6970-8731 UNSPECIFIED Dannappel, Marius UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarzer, Robin UNSPECIFIED UNSPECIFIED UNSPECIFIED Welz, Patrick UNSPECIFIED UNSPECIFIED UNSPECIFIED Corona, Teresa UNSPECIFIED UNSPECIFIED UNSPECIFIED Walczak, Henning UNSPECIFIED orcid.org/0000-0002-6312-4591 UNSPECIFIED Weih, Falk UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Ulf UNSPECIFIED UNSPECIFIED UNSPECIFIED Kelliher, Michelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Pasparakis, Manolis UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-281423
DOI:	10.1016/j.immuni.2016.02.020
Journal or Publication Title:	Immunity
Volume:	44
Number:	3
Page Range:	S. 553 - 568
Date:	2016
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4180
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ANHIDROTIC ECTODERMAL DYSPLASIA; NLRP3 INFLAMMASOME; IKK-BETA; HOMEOSTASIS; APOPTOSIS; ACTIVATION; EXPRESSION; CASPASE-8; MUTATION; NECROSIS Multiple languages Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28142