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

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

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1
Centre for Functional Genomics and Human Disease, Monash Institute of Medical Research, Monash University, Clayton 3168, Australia.

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.

PMID:
16311601
DOI:
10.1038/ni1287
[Indexed for MEDLINE]
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