| Micro-RNA dysregulation in multiple sclerosis favours pro-inflammatory T-cell-mediated autoimmunity. | |
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MedLine Citation:
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PMID: 22088562 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Pro-inflammatory T cells mediate autoimmune demyelination in multiple sclerosis. However, the factors driving their development and multiple sclerosis susceptibility are incompletely understood. We investigated how micro-RNAs, newly described as post-transcriptional regulators of gene expression, contribute to pathogenic T-cell differentiation in multiple sclerosis. miR-128 and miR-27b were increased in naïve and miR-340 in memory CD4(+) T cells from patients with multiple sclerosis, inhibiting Th2 cell development and favouring pro-inflammatory Th1 responses. These effects were mediated by direct suppression of B lymphoma Mo-MLV insertion region 1 homolog (BMI1) and interleukin-4 (IL4) expression, resulting in decreased GATA3 levels, and a Th2 to Th1 cytokine shift. Gain-of-function experiments with these micro-RNAs enhanced the encephalitogenic potential of myelin-specific T cells in experimental autoimmune encephalomyelitis. In addition, treatment of multiple sclerosis patient T cells with oligonucleotide micro-RNA inhibitors led to the restoration of Th2 responses. These data illustrate the biological significance and therapeutic potential of these micro-RNAs in regulating T-cell phenotypes in multiple sclerosis. |
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Authors:
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Mireia Guerau-de-Arellano; Kristen M Smith; Jakub Godlewski; Yue Liu; Ryan Winger; Sean E Lawler; Caroline C Whitacre; Michael K Racke; Amy E Lovett-Racke |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-15 |
Journal Detail:
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Title: Brain : a journal of neurology Volume: - ISSN: 1460-2156 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372537 Medline TA: Brain Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1 Department of Neurology, The Ohio State University, 395 West 12th Avenue Columbus, OH 43210, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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