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

• Published in: Nature Immunology 2006-01, Vol.7 (1), p.33-39
• Main Authors: Hertzog, Paul J, Fenner, Jennifer E, Starr, Robyn, Cornish, Ann L, Zhang, Jian-Guo, Metcalf, Donald, Schreiber, Robert D, Sheehan, Kathleen, Hilton, Douglas J, Alexander, Warren S
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Biomedical and Life Sciences; Biomedicine; Blotting, Southern; Carrier Proteins - immunology; Carrier Proteins - metabolism; Immune response; Immunology; Immunoprecipitation; Infectious Diseases; 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
• ISSN: 1529-2908; 1529-2916; 1365-2567
• DOI: 10.1038/ni1287

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-α and IFN-β) and mice deficient in interferon-γ 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-γ. 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.