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Selected Publication:

Type of publication: Journal Article
Type of document: Full Paper

Year: 2015

Authors: Rauch, I; Rosebrock, F; Hainzl, E; Heider, S; Majoros, A; Wienerroither, S; Strobl, B; Stockinger, S; Kenner, L; Müller, M; Decker, T

Title: Noncanonical Effects of IRF9 in Intestinal Inflammation: More than Type I and Type III Interferons.

Source: Mol Cell Biol. 2015; 35(13):2332-2343

Authors Vetmeduni Vienna:

Hainzl Eva
Kenner Lukas
Müller Mathias
Stockinger Silvia
Strobl Birgit

Vetmed Research Units
Institute of Animal Breeding and Genetics, Unit of Molecular Genetics

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-α and IFN-β and type III interferons (IFN-III), also called IFN-λ. 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-λ as a potentially anticolitogenic cytokine and propose an important role for IRF9 as a component of noncanonical Stat complexes in the development of colitis.

Keywords Pubmed: Animals
Cells, Cultured
Chemokine CXCL10/genetics
Chemokine CXCL10/immunology
Colitis/chemically induced
Dextran Sulfate
Gene Deletion
Gene Expression Regulation
Interferon-Stimulated Gene Factor 3, gamma Subunit/genetics*
Interferon-Stimulated Gene Factor 3, gamma Subunit/immunology*
Mice, Inbred BALB C
Mice, Inbred C57BL
Promoter Regions, Genetic
Receptors, Interferon/genetics
Receptors, Interferon/immunology
STAT1 Transcription Factor/immunology
Signal Transduction

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