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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2006-12-4
pubmed:abstractText
Suppressors of cytokine signaling (SOCS) proteins are negative regulators of cytokine signaling by inhibiting the JAK-STAT signal transduction pathway, but their role in innate immunity remains to be investigated. In the present study, we demonstrate that overexpression of SOCS5 in T cells augments innate immunity during septic peritonitis induced by cecal ligation and puncture (CLP). Mice with a cell-specific overexpression of SOCS5 in T cells (SOCS5 transgenic (Tg)) were resistant to the lethality relative to the wild-type (WT) mice. This was most likely due to the enhanced innate immunity in SOCS5Tg mice, as bacterial burden in SOCS5Tg mice was significantly lower than WT mice. Accumulation of neutrophils and macrophages was augmented in SOCS5Tg mice, an event that was accompanied by increased peritoneal levels of IL-12, IFN-gamma, and TNF-alpha. In vitro bactericidal activities of macrophages and neutrophils were enhanced in SOCS5Tg mice. Both neutrophils and macrophages from WT mice adopted enhanced bacterial killing activity when cocultured with CD4+ T cells from SOCS5Tg mice, relative to CD4+ T cells from WT mice. Adoptive transfer of SOCS5Tg-CD4+ T cells into T- and B cell-deficient RAG-2(-/-) mice resulted in augmented leukocyte infiltration and increased peritoneal levels of IL-12, IFN-gamma, and TNF-alpha after CLP, as compared with the controls. Furthermore, CLP-induced bacterial burden in RAG-2(-/-) mice harboring SOCS5Tg-CD4+ T cells was significantly reduced relative to the controls. These findings provide evidence that intervention of SOCS5 expression in T cells affects innate immunity, which highlight a novel role of T cells during sepsis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
177
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8650-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Overexpression of suppressor of cytokine signaling-5 in T cells augments innate immunity during septic peritonitis.
pubmed:affiliation
Department of Pathology and Experimental Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't