| Silencing T-bet defines a critical role in the differentiation of autoreactive T lymphocytes. | |
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MedLine Citation:
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PMID: 15539157 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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As a means of developing therapies that target the pathogenic T cells in multiple sclerosis (MS) without compromising the immune system or eliciting systemic side effects, we investigated the use of T-bet-specific antisense oligonucleotides and small interfering RNAs (siRNA) to silence T-bet expression in autoreactive encephalitogenic T cells and evaluated the biological consequences of this suppression in experimental autoimmune encephalomyelitis, a model for MS. The T-bet-specific AS oligonucleotide and siRNA suppressed T-bet expression, IFNgamma production, and STAT1 levels during antigen-specific T cell differentiation. In vitro suppression of T-bet during differentiation of myelin-specific T cells and in vivo administration of a T-bet-specific antisense oligonucleotide or siRNA inhibited disease. T-bet was shown to bind the IFNgamma and STAT1 promoters, but did not regulate the IL-12/STAT4 pathway. Since T-bet regulates IFNgamma production in CD4(+) T cells, but to a lesser extent in most other IFNgamma-producing cells, T-bet may be a target for therapeutics for Th1-mediated diseases. |
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Authors:
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Amy E Lovett-Racke; Anne E Rocchini; Judy Choy; Sara C Northrop; Rehana Z Hussain; Robert B Ratts; Devanjan Sikder; Michael K Racke |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Immunity Volume: 21 ISSN: 1074-7613 ISO Abbreviation: Immunity Publication Date: 2004 Nov |
Date Detail:
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Created Date: 2004-11-12 Completed Date: 2004-12-15 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9432918 Medline TA: Immunity Country: United States |
Other Details:
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Languages: eng Pagination: 719-31 Citation Subset: IM |
Affiliation:
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Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 USA. amy.lovett-racke@utsouthwestern.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Differentiation DNA-Binding Proteins / genetics Encephalomyelitis, Autoimmune, Experimental / immunology, therapy Interferon-gamma / genetics Interleukin-12 / pharmacology Mice Oligonucleotides, Antisense / pharmacology RNA, Small Interfering / pharmacology Receptors, Interleukin / genetics Receptors, Interleukin-12 STAT1 Transcription Factor STAT4 Transcription Factor T-Box Domain Proteins T-Lymphocytes / cytology* Trans-Activators / genetics Transcription Factors / genetics, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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K24 NS044250/NS/NINDS NIH HHS; R01 NS037513/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; 0/Oligonucleotides, Antisense; 0/RNA, Small Interfering; 0/Receptors, Interleukin; 0/Receptors, Interleukin-12; 0/STAT1 Transcription Factor; 0/STAT4 Transcription Factor; 0/Stat1 protein, mouse; 0/Stat4 protein, mouse; 0/T-Box Domain Proteins; 0/T-box transcription factor TBX21; 0/Trans-Activators; 0/Transcription Factors; 187348-17-0/Interleukin-12; 82115-62-6/Interferon-gamma |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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