[HTML][HTML] SOCS1 is a critical inhibitor of interferon γ signaling and prevents the potentially fatal neonatal actions of this cytokine

WS Alexander, R Starr, JE Fenner, CL Scott… - Cell, 1999 - cell.com
WS Alexander, R Starr, JE Fenner, CL Scott, E Handman, NS Sprigg, JE Corbin, AL Cornish…
Cell, 1999cell.com
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 …
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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