| First Author | Rauch I | Year | 2015 |
| Journal | Mol Cell Biol | Volume | 35 |
| Issue | 13 | Pages | 2332-43 |
| PubMed ID | 25918247 | Mgi Jnum | J:224099 |
| Mgi Id | MGI:5661268 | Doi | 10.1128/MCB.01498-14 |
| Citation | Rauch I, et al. (2015) Noncanonical Effects of IRF9 in Intestinal Inflammation: More than Type I and Type III Interferons. Mol Cell Biol 35(13):2332-43 |
| abstractText | 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. |
