Source:http://linkedlifedata.com/resource/pubmed/id/15128803
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
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| pubmed:dateCreated |
2004-5-6
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| pubmed:abstractText |
An initial activation signal via the TCR in a restricted cytokine environment is critical for the onset of Th cell development. Cytokines regulate the expression of key transcriptional factors, T-bet and GATA-3, which instruct the direction of Th1 and Th2 differentiation, through changes in chromatin conformation. In this study, we investigated the kinetics of IL-4-mediated signaling in a transgenic mouse, expressing human IL-4R on a mouse IL-4alphaR-deficient background. These experiments, allowing induction with human IL-4 at defined times, demonstrated that an IL-4 signal was required at the early stage of TCR-mediated T cell activation for lineage commitment to Th2, along with structural changes in chromatin, which take place in the conserved noncoding sequence-1 and -2 within the IL-4 locus. At later times, however, IL-4 failed to promote efficient Th2 differentiation and decondensation of chromatin, even though GATA-3 was clearly induced in the nuclei by IL-4 stimulation. Moreover, IL-4-mediated Th2 instruction was independent from cell division mediated by initial TCR stimulation. The role of IL-4 signaling may have a time restriction during Th2 differentiation. In late stages of initial T cell activation, the chromatin structure of the IL-4 locus retains condensation state. These results demonstrate that IL-4-induced GATA-3 expression is time-restriction switch for Th2 differentiation.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/GATA3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/GATA3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Genetic Markers,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
172
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
6158-66
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:15128803-Animals,
pubmed-meshheading:15128803-Cell Differentiation,
pubmed-meshheading:15128803-Cell Division,
pubmed-meshheading:15128803-Cell Line,
pubmed-meshheading:15128803-Cell Lineage,
pubmed-meshheading:15128803-Cell Separation,
pubmed-meshheading:15128803-Chromatin,
pubmed-meshheading:15128803-Conserved Sequence,
pubmed-meshheading:15128803-GATA3 Transcription Factor,
pubmed-meshheading:15128803-Genetic Markers,
pubmed-meshheading:15128803-Humans,
pubmed-meshheading:15128803-Interleukin-4,
pubmed-meshheading:15128803-Kinetics,
pubmed-meshheading:15128803-Mice,
pubmed-meshheading:15128803-Mice, Inbred BALB C,
pubmed-meshheading:15128803-Mice, Knockout,
pubmed-meshheading:15128803-Mice, Transgenic,
pubmed-meshheading:15128803-Receptors, Interleukin-4,
pubmed-meshheading:15128803-Signal Transduction,
pubmed-meshheading:15128803-Th2 Cells,
pubmed-meshheading:15128803-Transcription Factors
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| pubmed:year |
2004
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| pubmed:articleTitle |
IL-4-induced GATA-3 expression is a time-restricted instruction switch for Th2 cell differentiation.
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| pubmed:affiliation |
Research Institute for Biological Sciences, Tokyo University of Science, Yamazaki, Noda City, Chiba, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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