Zeitschriftenaufsatz
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2015
Noncanonical Effects of IRF9 in Intestinal Inflammation: More than Type I and Type III Interferons
Autor:in
Rauch, Isabella; Rosebrock, Felix; Hainzl, Eva; Heider, Susanne; Majoros, Andrea; Wienerroither, Sebastian; Strobl, Birgit; Stockinger, Silvia; Kenner, Lukas; Mueller, Mathias; Decker, T.
Publikationen als Autor:in / Herausgeber:in der Vetmeduni
Journal
Abstrakt
The interferon (IFN)-stimulated gene factor 3 (ISGF3) transcription factor with its Stat1, Stat2, and interferon regulatory factor 9 (IRF9) subunits is employed for transcriptional responses downstream of receptors for type I interferons (IFN-I) that include IFN-alpha and IFN-beta and type III interferons (IFN-III), also called IFN-lambda. Here, we show in a murine model of dextran sodium sulfate (DSS)-induced colitis that IRF9 deficiency protects animals, whereas the combined loss of IFN-I and IFN-III receptors worsens their condition. We explain the different phenotypes by demonstrating a function of IRF9 in a noncanonical transcriptional complex with Stat1, apart from IFN-I and IFN-III signaling. Together, Stat1 and IRF9 produce a proinflammatory activity that overrides the benefits of the IFN-III response on intestinal epithelial cells. Our results further suggest that the CXCL10 chemokine gene is an important mediator of this proinflammatory activity. We thus establish IFN-lambda as a potentially anticolitogenic cytokine and propose an important role for IRF9 as a component of noncanonical Stat complexes in the development of colitis.
Schlagwörter
Animals; Cells, Cultured; Chemokine CXCL10/genetics; Chemokine CXCL10/immunology; Colitis/chemically induced; Colitis/genetics*; Colitis/immunology*; Colitis/pathology; Colon/immunology; Colon/pathology; Dextran Sulfate; Gene Deletion; Gene Expression Regulation; Interferon-Stimulated Gene Factor 3, gamma Subunit/genetics*; Interferon-Stimulated Gene Factor 3, gamma Subunit/immunology*; Interferons/immunology*; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Promoter Regions, Genetic; Receptors, Interferon/genetics; Receptors, Interferon/immunology; STAT1 Transcription Factor/immunology; Signal Transduction;
Dokumententyp
Originalarbeit
ISSN/eISSN
0270-7306 - 1098-5549
10.1128/MCB.01498-14
WoS ID
PubMed ID