Universität zu Köln

Eftychi, Christina, Schwarzer, Robin, Vlantis, Katerina, Wachsmuth, Laurens, Basic, Marijana, Wagle, Prerana, Neurath, Markus F., Becker, Christoph, Bleich, Andre and Pasparakis, Manolis ORCID: 0000-0002-9870-0966 (2019). Temporally Distinct Functions of the Cytokines IL-12 and IL-23 Drive Chronic Colon Inflammation in Response to Intestinal Barrier Impairment. Immunity, 51 (2). S. 367 - 385. CAMBRIDGE: CELL PRESS. ISSN 1097-4180

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Abstract

Epithelial barrier defects are implicated in the pathogenesis of inflammatory bowel disease (IBD); however, the role of microbiome dysbiosis and the cytokine networks orchestrating chronic intestinal inflammation in response to barrier impairment remain poorly understood. Here, we showed that altered Schaedler flora (ASF), a benign minimal microbiota, was sufficient to trigger colitis in a mouse model of intestinal barrier impairment. Colitis development required myeloid-cell-specific adaptor protein MyD88 signaling and was orchestrated by the cytokines IL-12, IL-23, and IFN-gamma. Colon inflammation was driven by IL-12 during the early stages of the disease, but as the mice aged, the pathology shifted toward an IL-23-dependent inflammatory response driving disease chronicity. These findings reveal that IL-12 and IL-23 act in a temporally distinct, biphasic manner to induce microbiota-driven chronic intestinal inflammation. Similar mechanisms might contribute to the pathogenesis of IBD particularly in patients with underlying intestinal barrier defects.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Eftychi, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarzer, Robin UNSPECIFIED UNSPECIFIED UNSPECIFIED Vlantis, Katerina UNSPECIFIED UNSPECIFIED UNSPECIFIED Wachsmuth, Laurens UNSPECIFIED UNSPECIFIED UNSPECIFIED Basic, Marijana UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagle, Prerana UNSPECIFIED UNSPECIFIED UNSPECIFIED Neurath, Markus F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Bleich, Andre UNSPECIFIED UNSPECIFIED UNSPECIFIED Pasparakis, Manolis UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-144059
DOI:	10.1016/j.immuni.2019.06.008
Journal or Publication Title:	Immunity
Volume:	51
Number:	2
Page Range:	S. 367 - 385
Date:	2019
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 ROR-GAMMA-T; CROHNS-DISEASE; EXPERIMENTAL COLITIS; GENETIC-BASIS; IFN-GAMMA; MUCOSAL; INTERLEUKIN-12; INNATE; MICE; PERMEABILITY Multiple languages Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14405