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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2003-1-8
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pubmed:abstractText |
Suppressor of cytokine signaling (SOCS)-1 is a member of a family of proteins that negatively regulate cytokine signaling pathways. We have previously established that SOCS-1 is a key regulator of IFN-gamma signaling and that IFN-gamma is responsible for the complex inflammatory disease that leads to the death of SOCS-1-deficient mice. In this study, we provide evidence that SOCS-1 is also a critical regulator of IFN-gamma-independent immunoregulatory factors. Mice lacking both SOCS-1 and IFN-gamma, although outwardly healthy, have clear abnormalities in their immune system, including a reduced ratio of CD4:CD8 T cells in lymphoid tissues and increased expression of T cell activation markers. To examine the contribution of TCR Ag specificity to these immune defects, we have generated two lines of SOCS-1-deficient mice expressing a transgenic TCR specific for an exogenous Ag, OVA (OT-I and OT-II). Although TCR transgenic SOCS-1(-/-) mice have a longer lifespan than nontransgenic SOCS-1(-/-) mice, they still die as young adults with inflammatory disease and the TCR transgenic SOCS-1(-/-) T cells appear activated despite the absence of OVA. This suggests that both Ag-dependent and -independent mechanisms contribute to the disease in SOCS-1-deficient mice. Thus, SOCS-1 is a critical regulator of T cell activation and homeostasis, and its influence extends beyond regulating IFN-gamma signaling.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, T-Lymphocyte,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Socs1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Suppressor of Cytokine Signaling...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0022-1767
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pubmed:author |
pubmed-author:AlexanderWarren SWS,
pubmed-author:CorbinJason EJE,
pubmed-author:CornishAnn LAL,
pubmed-author:DarwicheRimaR,
pubmed-author:DaveyGayle MGM,
pubmed-author:DuaG LGL,
pubmed-author:GodfreyDale IDI,
pubmed-author:GreenhalghChristopher JCJ,
pubmed-author:HeathWilliam RWR,
pubmed-author:HiltonDouglas JDJ,
pubmed-author:MetcalfDonaldD,
pubmed-author:NicolaNicos ANA,
pubmed-author:PurtonJared FJF,
pubmed-author:StarrRobynR
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
170
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
878-86
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12517953-Animals,
pubmed-meshheading:12517953-CD4-CD8 Ratio,
pubmed-meshheading:12517953-Carrier Proteins,
pubmed-meshheading:12517953-Cytokines,
pubmed-meshheading:12517953-Epitopes, T-Lymphocyte,
pubmed-meshheading:12517953-Fetus,
pubmed-meshheading:12517953-Homeostasis,
pubmed-meshheading:12517953-Immunophenotyping,
pubmed-meshheading:12517953-Interferon-gamma,
pubmed-meshheading:12517953-Lymphatic Diseases,
pubmed-meshheading:12517953-Lymphocyte Activation,
pubmed-meshheading:12517953-Mice,
pubmed-meshheading:12517953-Mice, Inbred BALB C,
pubmed-meshheading:12517953-Mice, Inbred C57BL,
pubmed-meshheading:12517953-Mice, Knockout,
pubmed-meshheading:12517953-Mice, Transgenic,
pubmed-meshheading:12517953-Organ Culture Techniques,
pubmed-meshheading:12517953-Receptors, Antigen, T-Cell,
pubmed-meshheading:12517953-Repressor Proteins,
pubmed-meshheading:12517953-Signal Transduction,
pubmed-meshheading:12517953-Suppressor of Cytokine Signaling Proteins,
pubmed-meshheading:12517953-T-Lymphocyte Subsets,
pubmed-meshheading:12517953-Thymus Gland
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pubmed:year |
2003
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pubmed:articleTitle |
Suppressor of cytokine signaling-1 has IFN-gamma-independent actions in T cell homeostasis.
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pubmed:affiliation |
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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