Cell
Volume 98, Issue 5, 3 September 1999, Pages 597-608
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Article
SOCS1 Is a Critical Inhibitor of Interferon γ Signaling and Prevents the Potentially Fatal Neonatal Actions of this Cytokine

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Abstract

Mice lacking suppressor of cytokine signaling-1 (SOCS1) develop a complex fatal neonatal disease. In this study, SOCS1−/− mice were shown to exhibit excessive responses typical of those induced by interferon γ (IFNγ), were hyperresponsive to viral infection, and yielded macrophages with an enhanced IFNγ-dependent capacity to kill L. major parasites. The complex disease in SOCS1−/− mice was prevented by administration of anti-IFNγ antibodies and did not occur in SOCS1−/− mice also lacking the IFNγ gene. Although IFNγ is essential for resistance to a variety of infections, the potential toxic action of IFNγ, particularly in neonatal mice, appears to require regulation. Our data indicate that SOCS1 is a key modulator of IFNγ action, allowing the protective effects of this cytokine to occur without the risk of associated pathological responses.

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