Suppressor of cytokine signaling 1 regulates the immune response to infection by a unique inhibition of type I interferon activity

Nat Immunol. 2006 Jan;7(1):33-9. doi: 10.1038/ni1287. Epub 2005 Nov 27.


Suppressor of cytokine signaling 1 (SOCS1) is a critical regulator of cytokine signaling and immune responses. SOCS1-deficient mice develop severe inflammatory disease, but are very resistant to viral infections. Using neutralizing antibody to type I interferon (IFN-alpha and IFN-beta) and mice deficient in interferon-gamma or type I interferon receptor components (IFNAR1 or IFNAR2), we demonstrate here that SOCS1 deficiency amplified type I interferon antiviral and proinflammatory actions independently of interferon-gamma. The mechanism of the suppression of type I interferon responses by SOCS1 was distinct from that of other cytokines. SOCS1 associated with and regulated IFNAR1- but not IFNAR2-specific signals, abrogating tyrosine phosphorylation of transcription factor STAT1 and reducing the duration of antiviral gene expression. Thus, SOCS1 is an important in vivo inhibitor of type I interferon signaling and contributes to balancing its beneficial antiviral versus detrimental proinflammatory effects on innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Blotting, Southern
  • Carrier Proteins / immunology*
  • Carrier Proteins / metabolism
  • Immunoprecipitation
  • Interferon Type I / immunology*
  • Interferon Type I / metabolism
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Mice
  • Receptor, Interferon alpha-beta
  • Receptors, Interferon / immunology
  • Receptors, Interferon / metabolism
  • Repressor Proteins / immunology*
  • Repressor Proteins / metabolism
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins / immunology*
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • Transfection
  • Virus Diseases / immunology*


  • Carrier Proteins
  • Ifnar1 protein, mouse
  • Ifnar2 protein, mouse
  • Interferon Type I
  • Membrane Proteins
  • Receptors, Interferon
  • Repressor Proteins
  • Socs1 protein, mouse
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Receptor, Interferon alpha-beta