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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2010-5-31
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pubmed:abstractText |
T cell activation is tightly regulated to avoid autoimmunity. Gene related to anergy in lymphocytes (GRAIL, encoded by Rnf128) is an E3 ubiquitin ligase associated with T cell tolerance. Here, we generated and analyzed GRAIL-deficient mice and found they were resistant to immune tolerance induction and exhibited greater susceptibility to autoimmune diseases than wild-type mice. GRAIL-deficient naive T cells, after activation, exhibited increased proliferation and cytokine expression than controls and did not depend on costimulation for effector generation. Moreover, GRAIL-deficient regulatory T (Treg) cells displayed reduced suppressive function, associated with increased Th17 cell-related gene expression. GRAIL-deficient naive and Treg cells were less efficient in downregulating T cell receptor (TCR)-CD3 expression after activation and exhibited increased NFATc1 transcription factor expression; GRAIL expression promoted CD3 ubiquitinylation. Our results indicate that GRAIL, by mediating TCR-CD3 degradation, regulates naive T cell tolerance induction and Treg cell function.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-11571458,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-11907098,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-12121669,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-12646638,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-12705856,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-12879022,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-14973438,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-15187104,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-15210761,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-15240694,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-15252218,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-15306813,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-15780990,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-15879595,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-16424156,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-16724117,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-16864790,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-17114425,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-17239241,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-17259178,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-17581589,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-17617602,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-18585065,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-18641297,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20493730-19805371
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1097-4180
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pubmed:author |
pubmed-author:ChungYeonseokY,
pubmed-author:DongChenC,
pubmed-author:LinXinX,
pubmed-author:LozanoGuillerminaG,
pubmed-author:MartinezGustavo JGJ,
pubmed-author:NurievaRoza IRI,
pubmed-author:ReynoldsJoseph MJM,
pubmed-author:RoeP LPL,
pubmed-author:SunShao-CongSC,
pubmed-author:WangSung-LingSL,
pubmed-author:ZhangYongliangY,
pubmed-author:ZhengShulingS
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pubmed:copyrightInfo |
Copyright 2010 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
28
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pubmed:volume |
32
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
670-80
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pubmed:dateRevised |
2011-8-1
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pubmed:meshHeading |
pubmed-meshheading:20493730-Animals,
pubmed-meshheading:20493730-Antigens, CD3,
pubmed-meshheading:20493730-Gene Expression Regulation,
pubmed-meshheading:20493730-Immune Tolerance,
pubmed-meshheading:20493730-Immunoblotting,
pubmed-meshheading:20493730-Mice,
pubmed-meshheading:20493730-Mice, Knockout,
pubmed-meshheading:20493730-Receptors, Antigen, T-Cell,
pubmed-meshheading:20493730-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20493730-Signal Transduction,
pubmed-meshheading:20493730-T-Lymphocytes, Regulatory,
pubmed-meshheading:20493730-Ubiquitin-Protein Ligases
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pubmed:year |
2010
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pubmed:articleTitle |
The E3 ubiquitin ligase GRAIL regulates T cell tolerance and regulatory T cell function by mediating T cell receptor-CD3 degradation.
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pubmed:affiliation |
Department of Immunology, M.D. Anderson Cancer Center, Houston, TX 77030, USA. rnurieva@mdanderson.org
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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