Source:http://linkedlifedata.com/resource/pubmed/id/19841877
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2010-1-21
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| pubmed:abstractText |
CD4(+)CD25(+) regulatory T cells (Treg), a subpopulation of CD4(+) T cells, regulate immune responses. Foxp3 is a key transcription factor for the development and function of Treg cells. During T-cell activation in vitro, a DNA demethylation agent 5-Aza-2'-deoxycytydine (DAC) can induce Foxp3 expression in CD4(+)CD25(-) Foxp3(-) cells via altering methylation status of a conserved element in the 5'-untranslated region of the Foxp3 gene. However, the effects of this agent on the development of Foxp3(+) Treg cells in the thymus and in vivo are poorly understood. In the present study, a short-term treatment with a low dose of DAC significantly increased the ratios of thymic CD4(+)CD8(-) CD25(+) cells or CD4(+)CD8(-) Foxp3(+) cells to CD4(+)CD8(-) cells, and the total numbers of thymic CD4(+)CD8(-)Foxp3(+) Treg cells or CD4(+)CD8(-)CD25(+)Foxp3(+) Treg cells in the thymus in mice. DAC-treatment induced the Foxp3 expression and the significant demethylation of a CpG island in the first intron of the Foxp3 gene in CD4(+)CD8(-)CD25(+) cells predominantly. Furthermore, CD4(+)CD8(-)CD25(+) thymocytes in DAC-treated mice exhibited enhanced immunosuppressive function than those in control mice. In addition, DAC treatment in vivo was effective in improving the clinical course of diabetes in cyclophosphamide (CY)-potentiated non-obese diabetic mice (CY-NOD). Thus, the in vivo treatment with DAC can significantly promote the development of natural thymic CD4(+)CD25(+)Foxp3(+) Treg cells through Foxp3 demethylation, implicating a therapeutic application of DAC in patients suffering from autoimmune diseases.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Azacitidine,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Foxp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2 Receptor alpha Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/decitabine
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
|
| pubmed:issn |
1432-1440
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
87
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1191-205
|
| pubmed:dateRevised |
2011-7-8
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| pubmed:meshHeading |
pubmed-meshheading:19841877-Animals,
pubmed-meshheading:19841877-Azacitidine,
pubmed-meshheading:19841877-Base Sequence,
pubmed-meshheading:19841877-CD4-Positive T-Lymphocytes,
pubmed-meshheading:19841877-Diabetes Mellitus, Type 1,
pubmed-meshheading:19841877-Female,
pubmed-meshheading:19841877-Forkhead Transcription Factors,
pubmed-meshheading:19841877-Humans,
pubmed-meshheading:19841877-Interleukin-2 Receptor alpha Subunit,
pubmed-meshheading:19841877-Lymphocyte Activation,
pubmed-meshheading:19841877-Male,
pubmed-meshheading:19841877-Methylation,
pubmed-meshheading:19841877-Mice,
pubmed-meshheading:19841877-Mice, Inbred C57BL,
pubmed-meshheading:19841877-Mice, Inbred NOD,
pubmed-meshheading:19841877-Molecular Sequence Data,
pubmed-meshheading:19841877-T-Lymphocytes, Regulatory,
pubmed-meshheading:19841877-Thymus Gland,
pubmed-meshheading:19841877-Treatment Outcome
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| pubmed:year |
2009
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| pubmed:articleTitle |
Induction of Foxp3 demethylation increases regulatory CD4+CD25+ T cells and prevents the occurrence of diabetes in mice.
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| pubmed:affiliation |
Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Chaoyang, Beijing, China 100101.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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