Source:http://linkedlifedata.com/resource/pubmed/id/21440248
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2011-4-14
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pubmed:abstractText |
CD4(+) T cells play critical roles in the generation of protective immunity against a variety of pathogens. The main two types of effector CD4(+) T cells, Th1 and Th2 are characterized by their ability to produce signature cytokines. Among them, IL-10 is a multi-functional cytokine that plays a crucial role in maintaining the balance between immunity and tolerance. Although IL-10 is produced by both differentiated primary Th1 and Th2 cells, Th2 cells produce much higher levels of IL-10 upon stimulation. However, little information is available on the molecular mechanisms of IL-10 gene regulation at the transcriptional level. Interferon regulatory factor IRF4 is a member of the IRF family of transcription factors and plays critical roles in the development of CD4(+) T cells into Th2 cells. In this present study, we elucidate the underlying mechanism of IRF4 mediated IL-10 gene transcription in primary CD4(+) T cells. Th2 specific binding of IRF4 to the IRF4 responsive elements in IL-10 locus potentiated IL-10 expression in Th2 cells. Knockdown of IRF4 by siRNA decreased IL-10 expression level in Th2 cells. Nuclear translocation of IRF4 was much higher in Th2 cells upon stimulation, which contribute to maintain IL-10(high) phenotype of Th2 cells. Collectively, our results suggest that stimulation driven quantitative differences of IRF4 in the nucleus and its binding to IL-10 regulatory elements are crucial mechanisms to induce IL-10(high) gene expression in Th2 cells.
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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/IL10 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/interferon regulatory factor-4
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pubmed:status |
MEDLINE
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pubmed:issn |
1090-2163
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pubmed:author | |
pubmed:copyrightInfo |
2011 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
268
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
97-104
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pubmed:meshHeading |
pubmed-meshheading:21440248-Animals,
pubmed-meshheading:21440248-Blotting, Western,
pubmed-meshheading:21440248-Cell Differentiation,
pubmed-meshheading:21440248-Cell Line, Tumor,
pubmed-meshheading:21440248-Cell Nucleus,
pubmed-meshheading:21440248-Flow Cytometry,
pubmed-meshheading:21440248-Gene Expression Regulation,
pubmed-meshheading:21440248-HEK293 Cells,
pubmed-meshheading:21440248-Humans,
pubmed-meshheading:21440248-Interferon Regulatory Factors,
pubmed-meshheading:21440248-Interleukin-10,
pubmed-meshheading:21440248-Mice,
pubmed-meshheading:21440248-Mice, Inbred C57BL,
pubmed-meshheading:21440248-Mice, Knockout,
pubmed-meshheading:21440248-RNA,
pubmed-meshheading:21440248-RNA, Small Interfering,
pubmed-meshheading:21440248-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:21440248-Specific Pathogen-Free Organisms,
pubmed-meshheading:21440248-Th2 Cells,
pubmed-meshheading:21440248-Transcription, Genetic
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pubmed:year |
2011
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pubmed:articleTitle |
IRF4 regulates IL-10 gene expression in CD4(+) T cells through differential nuclear translocation.
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pubmed:affiliation |
School of Life Sciences and Immune Synapse Research Center, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712, Republic of Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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