Micro-RNA dysregulation in multiple sclerosis favours pro-inflammatory T-cell-mediated autoimmunity

Department of Neurology, The Ohio State University, 395 West 12th Avenue Columbus, OH 43210, USA.
Brain (Impact Factor: 9.2). 11/2011; 134(Pt 12):3578-89. DOI: 10.1093/brain/awr262
Source: PubMed


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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    • "Total RNA was isolated by the Trizol method (Invitrogen, Carlsbad, CA, USA) and heparinase treated as described [19]. Primary MCT miRNA expression profiling was performed at the OSU Nucleic Acid Shared Resource using the TaqMan Array Human miRNA Panel (Human A Cards, v.2, Applied Biosystems, Foster City, CA, USA) as described previously [20]. This panel assays the expression of 377 human miRNAs, 151 of whose mature sequences are 100% conserved between human and dog (Sanger miRBase v.12). "
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    BMC Cancer 02/2014; 14(1):84. DOI:10.1186/1471-2407-14-84 · 3.36 Impact Factor
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    • "Guerau-de-Arellano et al. [28] have shown that miRNAs such as miR-128 and miR-27b increased in naive T cells and miR-340 in memory CD4 + T cells of MS patients are involved in differentiation of pathogenic T cells. Changes in the expression of these miRNAs inhibited Th2 differentiation and induced pathogenic Th1 differentiation in mouse and human cells, suggesting that these miRNAs could regulate T-cell phenotypes in MS and thus have therapeutic potentials [28]. Other studies on miRNA in MS were listed in Table 1 and explained below. "
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    ABSTRACT: Multiple sclerosis (MS) is a chronic devastating disease of the central nervous system (CNS), which is reported to be the most common neuroinflammatory disorder of the young adults. Although the underlying etiology of MS is not completely elucidated, the number of patients and burden to societies increases worldwide. There are several CNS disorders that might have overlapping phenotypic manifestations with MS; therefore, reliable and accessible diagnostic test is highly desirable for differential diagnosis. MicroRNAs (miRNAs) are small regulatory RNAs that are proven to be master regulators of gene expression. Recently, several studies have shown potential roles for miRNAs in development, hemostasis and maturation of immune system, suggesting possible involvement of these regulatory elements in autoimmune diseases, such as MS. We reviewed recent literature to explore miRNAs that are reported to be involved in pathogenesis of MS and found some miRNAs that might have potentials as being diagnostic biomarkers.
    Advances in Neuroimmune Biology 02/2013; 4(Volume 4, Number 2 / 2013):67-76. DOI:10.3233/NIB-130053
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    • "It has been suggested that miR-155 expression in dendritic cells is required for development of inflammatory Th17 cells (O'Connell et al., 2010). miR-155 is also associated with several autoimmune diseases such as EAE (Murugaiyan et al., 2011), arthritis (Kurowska-Stolarska et al., 2011), systemic lupus erythematosus (SLE) (Leng et al., 2011), chronic gastritis, and colitis (Oertli et al., 2011). In contrast to these reports, expression of miR- 155 has been found to negatively regulate Th17 cells in acute coronary syndrome patients (Yao et al., 2011). "
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