Noncanonical effects of IRF9 in intestinal inflammation

More than type I and type III interferons

Isabella Rauch, Felix Rosebrock, Eva Hainzl, Susanne Heider, Andrea Majoros, Sebastian Wienerroither, Birgit Strobl, Silvia Stockinger, Lukas Kenner, Mathias Müller, Thomas Decker

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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-ß 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.

Original languageEnglish (US)
Pages (from-to)2332-2343
Number of pages12
JournalMolecular and Cellular Biology
Volume35
Issue number13
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Gamma Subunit Interferon-Stimulated Gene Factor 3
Interferon Type I
Interferons
Inflammation
Colitis
Interferon-Stimulated Gene Factor 3
Interferon alpha-beta Receptor
Interferon Receptors
Chemokine CXCL10
Dextran Sulfate

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Rauch, I., Rosebrock, F., Hainzl, E., Heider, S., Majoros, A., Wienerroither, S., ... Decker, T. (2015). Noncanonical effects of IRF9 in intestinal inflammation: More than type I and type III interferons. Molecular and Cellular Biology, 35(13), 2332-2343. https://doi.org/10.1128/MCB.01498-14

Noncanonical effects of IRF9 in intestinal inflammation : More than type I and type III interferons. / Rauch, Isabella; Rosebrock, Felix; Hainzl, Eva; Heider, Susanne; Majoros, Andrea; Wienerroither, Sebastian; Strobl, Birgit; Stockinger, Silvia; Kenner, Lukas; Müller, Mathias; Decker, Thomas.

In: Molecular and Cellular Biology, Vol. 35, No. 13, 01.01.2015, p. 2332-2343.

Research output: Contribution to journalArticle

Rauch, I, Rosebrock, F, Hainzl, E, Heider, S, Majoros, A, Wienerroither, S, Strobl, B, Stockinger, S, Kenner, L, Müller, M & Decker, T 2015, 'Noncanonical effects of IRF9 in intestinal inflammation: More than type I and type III interferons', Molecular and Cellular Biology, vol. 35, no. 13, pp. 2332-2343. https://doi.org/10.1128/MCB.01498-14
Rauch, Isabella ; Rosebrock, Felix ; Hainzl, Eva ; Heider, Susanne ; Majoros, Andrea ; Wienerroither, Sebastian ; Strobl, Birgit ; Stockinger, Silvia ; Kenner, Lukas ; Müller, Mathias ; Decker, Thomas. / Noncanonical effects of IRF9 in intestinal inflammation : More than type I and type III interferons. In: Molecular and Cellular Biology. 2015 ; Vol. 35, No. 13. pp. 2332-2343.
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