SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine

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 gamma (IFNgamma), were hyperresponsive to viral infection, and yielded macrophages with an e...

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Bibliographic Details
Published in:Cell 1999-09, Vol.98 (5), p.597-608
Main Authors: Alexander, W S, Starr, R, Fenner, J E, Scott, C L, Handman, E, Sprigg, N S, Corbin, J E, Cornish, A L, Darwiche, R, Owczarek, C M, Kay, T W, Nicola, N A, Hertzog, P J, Metcalf, D, Hilton, D J
Format: Article
Language:English
Subjects:
Alphavirus Infections - mortality
Alphavirus Infections - prevention & control
Animals
Carrier Proteins - physiology
Disease Susceptibility
Gene Expression Regulation, Developmental
Interferon-gamma - antagonists & inhibitors
Interferon-gamma - pharmacology
Interferon-gamma - physiology
Leishmania major - immunology
Leishmaniasis - mortality
Leishmaniasis - prevention & control
Lymphopenia - mortality
Lymphopenia - prevention & control
Macrophages - drug effects
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Repressor Proteins
Semliki forest virus - immunology
Semliki forest virus - metabolism
Signal Transduction
Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling Proteins
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Summary: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 gamma (IFNgamma), were hyperresponsive to viral infection, and yielded macrophages with an enhanced IFNgamma-dependent capacity to kill L. major parasites. The complex disease in SOCS1-/- mice was prevented by administration of anti-IFNgamma antibodies and did not occur in SOCS1-/- mice also lacking the IFNgamma gene. Although IFNgamma is essential for resistance to a variety of infections, the potential toxic action of IFNgamma, particularly in neonatal mice, appears to require regulation. Our data indicate that SOCS1 is a key modulator of IFNgamma action, allowing the protective effects of this cytokine to occur without the risk of associated pathological responses.
ISSN:0092-8674
1097-4172
DOI:10.1016/S0092-8674(00)80047-1