Positive feedback regulation of type I interferon by the interferon-stimulated gene STING

EMBO Rep. 2015 Feb;16(2):202-12. doi: 10.15252/embr.201439366. Epub 2015 Jan 8.

Abstract

Stimulator of interferon genes (STING) is an important regulator of the innate immune response to cytoplasmic DNA. However, regulation of STING itself is largely unknown. Here, we show that STING transcription is induced by innate immune activators, such as cyclic dinucleotides (CDNs), through an IFNAR1- and STAT1-dependent pathway. We also identify a STAT1 binding site in the STING promoter that contributes to the activation of STING transcription. Furthermore, we show that induction of STING mediates the positive feedback regulation of CDN-triggered IFN-I. Thus, our study demonstrates that STING is an interferon-stimulated gene (ISG) and its induction is crucial for the IFN-I positive feedback loop.

Keywords: CDN; IFN; ISG; STING; cGAMP.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Binding Sites
  • Cell Line
  • Immunity, Innate / genetics
  • Interferon Type I / genetics
  • Interferon Type I / metabolism*
  • Interferons / metabolism*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Promoter Regions, Genetic / genetics
  • Receptor, Interferon alpha-beta / genetics
  • Receptor, Interferon alpha-beta / metabolism
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism

Substances

  • Interferon Type I
  • Membrane Proteins
  • STAT1 Transcription Factor
  • STING1 protein, human
  • Sting1 protein, mouse
  • Receptor, Interferon alpha-beta
  • Interferons