MicroRNAs miR-17 and miR-20a inhibit T cell activation genes and are under-expressed in MS whole blood

Matthew B. Cox, Murray J. Cairns, Melanie Bahlo, Helmut Butzkueven, Matthew A. Brown, Simon J. Foote, Lyn Griffiths, Trevor J. Kilpatrick, Pablo Moscato, Victoria M. Perreau, Justin P. Rubio, Jim Stankovich, Kaushal S. Gandhi, Bruce V. Taylor, James Wiley, Robert N. Heard, Adam P. Carroll, Sophia Moscovis, Graeme J. Stewart, Simon A. Broadley & 3 others Rodney J. Scott, David R. Booth, Jeanette Lechner-Scott

Research output: Contribution to journalArticle

176 Citations (Scopus)

Abstract

It is well established that Multiple Sclerosis (MS) is an immune mediated disease. Little is known about what drives the differential control of the immune system in MS patients compared to unaffected individuals. MicroRNAs (miRNAs) are small non-coding nucleic acids that are involved in the control of gene expression. Their potential role in T cell activation and neurodegenerative disease has recently been recognised and they are therefore excellent candidates for further studies in MS. We investigated the transcriptome of currently known miRNAs using miRNA microarray analysis in peripheral blood samples of 59 treatment nai{dotless}̈ve MS patients and 37 controls. Of these 59, 18 had a primary progressive, 17 a secondary progressive and 24 a relapsing remitting disease course. In all MS subtypes miR-17 and miR-20a were significantly underexpressed in MS, confirmed by RT-PCR. We demonstrate that these miRNAs modulate T cell activation genes in a knock-in and knock-down T cell model. The same T cell activation genes are also up-regulated in MS whole blood mRNA, suggesting these miRNAs or their analogues may provide useful targets for new therapeutic approaches.
Original languageEnglish
Article numbere12132
Number of pages7
JournalPLoS ONE
Volume5
Issue number8
DOIs
Publication statusPublished - 2010
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2010. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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