SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine
- Author(s)
- Alexander, WS; Starr, R; Fenner, JE; Scott, GL; Handman, E; Sprigg, NS; Corbin, JE; Cornish, AL; Darwiche, R; Owczarek, CM; Kay, TWH; Nicola, NA; Hertzog, PJ; Metcalf, D; Hilton, DJ;
- Details
- Publication Year 1999-09-03,Volume 98,Issue #5,Page 597-608
- Journal Title
- CELL
- Publication Type
- Journal Article
- 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 gamma (IFN gamma), were hyperresponsive to viral infection, and yielded macrophages with an enhanced IFN gamma-dependent capacity to kill L. major parasites. The complex disease in SOCS1(-/-) mice was prevented by administration of anti-IFN gamma antibodies and did not occur in SOCS1(-/-) mice also lacking the IFN gamma gene. Although IFN gamma is essential for resistance to a variety of infections, the potential toxic action of IFN gamma, particularly in neonatal mice, appears to require regulation. Our data indicate that SOCS1 is a key modulator of IFN gamma action, allowing the protective effects of this cytokine to occur without the risk of associated pathological responses.
- Publisher
- CELL PRESS
- Keywords
- JAK-STAT PATHWAY; MUTANT-CELL LINE; IFN-GAMMA; TARGETED DISRUPTION; TYROSINE PHOSPHORYLATION; SUCKLING MICE; RECEPTOR; PROTEIN; GENE; ACTIVATION
- Publisher's Version
- https://doi.org/10.1016/S0092-8674(00)80047-1
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1999-09-03 12:00:00