Twist mediates suppression of inflammation by type I IFNs and Axl

M. Nusrat Sharif, Dražen Šošić, Carla V. Rothlin, Erin Kelly, Greg Lemke, Eric N. Olson, Lionel B. Ivashkiv

Research output: Contribution to journalArticle

148 Scopus citations

Abstract

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 TNFα 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 TNFα production by immune complexes, Fc receptors, and Toll-like receptors. Suppression of TNFα 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-κB-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 TNFα production by antiinflammatory factors and pathways, and provide a mechanism by which type I IFNs and Axl receptors suppress inflammatory cytokine production. JEM

Original languageEnglish (US)
Pages (from-to)1891-1901
Number of pages11
JournalJournal of Experimental Medicine
Volume203
Issue number8
DOIs
StatePublished - Aug 7 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Sharif, M. N., Šošić, D., Rothlin, C. V., Kelly, E., Lemke, G., Olson, E. N., & Ivashkiv, L. B. (2006). Twist mediates suppression of inflammation by type I IFNs and Axl. Journal of Experimental Medicine, 203(8), 1891-1901. https://doi.org/10.1084/jem.20051725