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:
CreatorsEmailORCIDORCID Put Code
Eftychi, ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwarzer, RobinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vlantis, KaterinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wachsmuth, LaurensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Basic, MarijanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagle, PreranaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neurath, Markus F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bleich, AndreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pasparakis, ManolisUNSPECIFIEDorcid.org/0000-0002-9870-0966UNSPECIFIED
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:
KeywordsLanguage
ROR-GAMMA-T; CROHNS-DISEASE; EXPERIMENTAL COLITIS; GENETIC-BASIS; IFN-GAMMA; MUCOSAL; INTERLEUKIN-12; INNATE; MICE; PERMEABILITYMultiple languages
ImmunologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14405

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