| First Author | Sharif MN | Year | 2006 |
| Journal | J Exp Med | Volume | 203 |
| Issue | 8 | Pages | 1891-901 |
| PubMed ID | 16831897 | Mgi Jnum | J:124396 |
| Mgi Id | MGI:3721468 | Doi | 10.1084/jem.20051725 |
| Citation | Sharif MN, et al. (2006) Twist mediates suppression of inflammation by type I IFNs and Axl. J Exp Med 203(8):1891-901 |
| abstractText | Type I interferons (IFNs) are pleiotropic cytokines with antiviral and immunomodulatory properties. The immunosuppressive actions of type I IFNs are poorly understood, but IFN-mediated suppression of TNFalpha production has been implicated in the regulation of inflammation and contributes to the effectiveness of type I IFNs in the treatment of certain autoimmune and inflammatory diseases. In this study, we investigated mechanisms by which type I IFNs suppress induction of TNFalpha production by immune complexes, Fc receptors, and Toll-like receptors. Suppression of TNFalpha production was mediated by induction and activation of the Axl receptor tyrosine kinase and downstream induction of Twist transcriptional repressors that bind to E box elements in the TNF promoter and suppress NF-kappaB-dependent transcription. Twist expression was activated by the Axl ligand Gas6 and by protein S and apoptotic cells. These results implicate Twist proteins in regulation of TNFalpha production by antiinflammatory factors and pathways, and provide a mechanism by which type I IFNs and Axl receptors suppress inflammatory cytokine production. |
