Source:http://linkedlifedata.com/resource/pubmed/id/18768844
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
2008-9-4
|
| pubmed:abstractText |
STAT5 molecules are key components of the IL-2 signaling pathway, the deficiency of which often results in autoimmune pathology due to a reduced number of CD4(+)CD25(+) naturally occurring regulatory T (Treg) cells. One of the consequences of the IL-2-STAT5 signaling axis is up-regulation of FOXP3, a master control gene for naturally occurring Treg cells. However, the roles of STAT5 in other Treg subsets have not yet been elucidated. We recently demonstrated that IL-2 enhanced IL-10 production through STAT5 activation. This occurred in two types of human Treg cells: a novel type of umbilical cord blood-derived Treg cell, termed HOZOT, and Tr1-like Treg cells, IL-10-Treg. In this study, we examined the regulatory mechanisms of IL-10 production in these Treg cells, focusing specifically on the roles of STAT5. By performing bioinformatic analysis on the IL-10 locus, we identified one STAT-responsive element within intron 4, designated I-SRE-4, as an interspecies-conserved sequence. We found that I-SRE-4 acted as an enhancer element, and clustered CpGs around the I-SRE-4 were hypomethylated in IL-10-producing Treg cells, but not in other T cells. A gel-shift analysis using a nuclear extract from IL-2-stimulated HOZOT confirmed that CpG DNA methylation around I-SRE-4 reduced STAT5 binding to the element. Chromatin immunoprecipitation analysis revealed the in situ binding of IL-2-activated STAT5 to I-SRE-4. Thus, we provide molecular evidence for the involvement of an IL-2-STAT5 signaling axis in the expression of IL-10 by human Treg cells, an axis that is regulated by the intronic enhancer, I-SRE-4, and epigenetic modification of this element.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
1550-6606
|
| pubmed:author |
pubmed-author:HarashimaAkiraA,
pubmed-author:InoueToshiyaT,
pubmed-author:KibataMasayoshiM,
pubmed-author:NakamuraShujiS,
pubmed-author:OkochiAyumiA,
pubmed-author:OtaniTakeshiT,
pubmed-author:SugimotoAkiraA,
pubmed-author:SuzukiMotoyukiM,
pubmed-author:TakeuchiMakotoM,
pubmed-author:TorayaTerumasaT,
pubmed-author:Tsuji-TakayamaKazueK,
pubmed-author:YamamotoMayukoM,
pubmed-author:YamasakiFumiyukiF
|
| pubmed:issnType |
Electronic
|
| pubmed:day |
15
|
| pubmed:volume |
181
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3897-905
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:18768844-Animals,
pubmed-meshheading:18768844-Base Sequence,
pubmed-meshheading:18768844-Cell Line, Tumor,
pubmed-meshheading:18768844-Cells, Cultured,
pubmed-meshheading:18768844-Coculture Techniques,
pubmed-meshheading:18768844-Conserved Sequence,
pubmed-meshheading:18768844-Enhancer Elements, Genetic,
pubmed-meshheading:18768844-Epigenesis, Genetic,
pubmed-meshheading:18768844-Humans,
pubmed-meshheading:18768844-Interleukin-10,
pubmed-meshheading:18768844-Interleukin-2,
pubmed-meshheading:18768844-Introns,
pubmed-meshheading:18768844-Mice,
pubmed-meshheading:18768844-Molecular Sequence Data,
pubmed-meshheading:18768844-Protein Binding,
pubmed-meshheading:18768844-Response Elements,
pubmed-meshheading:18768844-STAT5 Transcription Factor,
pubmed-meshheading:18768844-Signal Transduction,
pubmed-meshheading:18768844-T-Lymphocytes, Regulatory
|
| pubmed:year |
2008
|
| pubmed:articleTitle |
The production of IL-10 by human regulatory T cells is enhanced by IL-2 through a STAT5-responsive intronic enhancer in the IL-10 locus.
|
| pubmed:affiliation |
Cell Biology Institute, Research Center, Hayashibara Biochemical Laboratories, Fujisaki, Okayama, Japan.
|
| pubmed:publicationType |
Journal Article,
Comparative Study
|