Suppressor of cytokine signaling 1 regulates the immune response to infection by a unique inhibition of type I interferon activity
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
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2006-01-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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