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

Jennifer E. Fenner, Robyn Starr, Ann L. Cornish, Jian Guo Zhang, Donald Metcalf, Robert D. Schreiber, Kathleen Sheehan, Douglas J. Hilton, Warren S. Alexander, Paul J. Hertzog

Research output: Contribution to journalArticle

196 Scopus citations

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-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.

Original languageEnglish
Pages (from-to)33-39
Number of pages7
JournalNature immunology
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2006

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    Fenner, J. E., Starr, R., Cornish, A. L., Zhang, J. G., Metcalf, D., Schreiber, R. D., Sheehan, K., Hilton, D. J., Alexander, W. S., & Hertzog, P. J. (2006). Suppressor of cytokine signaling 1 regulates the immune response to infection by a unique inhibition of type I interferon activity. Nature immunology, 7(1), 33-39. https://doi.org/10.1038/ni1287