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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
25
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pubmed:dateCreated |
2008-6-16
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pubmed:abstractText |
The cytokine, transforming growth factor-beta1 (TGF-beta1), converts naive T cells into regulatory T cells that prevent autoimmunity. However, in the presence of interleukin (IL)-6, TGF-beta1 has also been found to promote differentiation into IL-17-producing helper T (Th17) cells that are deeply involved in autoimmunity and inflammation. However, it has not been clarified how TGF-beta1 and IL-6 determine such a distinct fate. Here we found that a master regulator for Th17, retinoic acid-related orphan receptor gammat (RORgammat), was rapidly induced by TGF-beta1 regardless of the presence of IL-6. IL-6 reduced Foxp3 expression, and overexpression of Foxp3 in a T cell line resulted in a strong reduction of IL-17A expression. We have characterized the IL-17A promoter and found that RORgammat binding is sufficient for activation of the minimum promoter in the HEK 293T cells. RORgammat-mediated IL-17A promoter activation was suppressed by forced expression of Foxp3. Foxp3 directly interacted with RORgammat through exon 2 region of Foxp3. The exon 2 region and forkhead (FKH) domain of Foxp3 were necessary for the suppression of RORgammat-mediated IL-17A promoter activation. We propose that induction of Foxp3 is the mechanism for the suppression of Th17 and polarization into inducible Treg.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/FOXP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-17,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Subfamily 1...,
http://linkedlifedata.com/resource/pubmed/chemical/RORC protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Thyroid Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Rorc protein, mouse
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
20
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pubmed:volume |
283
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
17003-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18434325-Animals,
pubmed-meshheading:18434325-Base Sequence,
pubmed-meshheading:18434325-Binding Sites,
pubmed-meshheading:18434325-Forkhead Transcription Factors,
pubmed-meshheading:18434325-Humans,
pubmed-meshheading:18434325-Interleukin-17,
pubmed-meshheading:18434325-Mice,
pubmed-meshheading:18434325-Models, Biological,
pubmed-meshheading:18434325-Molecular Sequence Data,
pubmed-meshheading:18434325-Nuclear Receptor Subfamily 1, Group F, Member 3,
pubmed-meshheading:18434325-Promoter Regions, Genetic,
pubmed-meshheading:18434325-Protein Binding,
pubmed-meshheading:18434325-Receptors, Retinoic Acid,
pubmed-meshheading:18434325-Receptors, Thyroid Hormone,
pubmed-meshheading:18434325-Sequence Homology, Nucleic Acid,
pubmed-meshheading:18434325-T-Lymphocytes,
pubmed-meshheading:18434325-Transcription, Genetic
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pubmed:year |
2008
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pubmed:articleTitle |
Foxp3 inhibits RORgammat-mediated IL-17A mRNA transcription through direct interaction with RORgammat.
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pubmed:affiliation |
Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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