Dynamic control of type I IFN signalling by an integrated network of negative regulators

Trends Immunol. 2015 Mar;36(3):150-60. doi: 10.1016/j.it.2015.02.002. Epub 2015 Feb 25.


Whereas type I interferons (IFNs) have critical roles in protection from pathogens, excessive IFN responses contribute to pathology in both acute and chronic settings, pointing to the importance of balancing activating signals with regulatory mechanisms that appropriately tune the response. Here we review evidence for an integrated network of negative regulators of IFN production and action, which function at all levels of the activating and effector signalling pathways. We propose that the aim of this extensive network is to limit tissue damage while enabling an IFN response that is temporally appropriate and of sufficient magnitude. Understanding the architecture and dynamics of this network, and how it differs in distinct tissues, will provide new insights into IFN biology and aid the design of more effective therapeutics.

Keywords: Interferon; JAK; SOCS; STAT; cytokine.

Publication types

  • Review

MeSH terms

  • Dendritic Cells / immunology
  • Feedback, Physiological
  • Gene Expression Regulation / immunology
  • Gene Regulatory Networks / immunology
  • Humans
  • Immunity, Innate*
  • Interferon Type I / genetics
  • Interferon Type I / immunology*
  • Interleukins / genetics
  • Interleukins / immunology
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / immunology*
  • MicroRNAs / genetics
  • MicroRNAs / immunology*
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / immunology
  • Signal Transduction
  • Smad Proteins / genetics
  • Smad Proteins / immunology*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / immunology*
  • Viruses / immunology


  • Interferon Type I
  • Interleukins
  • Intracellular Signaling Peptides and Proteins
  • MicroRNAs
  • Receptors, Cytokine
  • Smad Proteins
  • Ubiquitin-Protein Ligases