Suppressor of cytokine signaling 1 regulates the immune response to infection by a unique inhibition of type I interferon activity
- Author(s)
- Fenner, JE; Starr, R; Cornish, AL; Zhang, JG; Metcalf, D; Schreiber, RD; Sheehan, K; Hilton, DJ; Alexander, WS; Hertzog, PJ;
- Details
- Publication Year 2006-01,Volume 7,Issue #1,Page 33-39
- Journal Title
- NATURE IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- JANUS TYROSINE KINASE; SOCS BOX; INDUCIBLE GENE; SH2 DOMAIN; GAMMA; PROTEINS; RECEPTOR; CELLS; MICE; TRANSDUCTION
- Publisher's Version
- https://doi.org/10.1038/ni1287
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2006-01-01 12:00:00