Altered miRNA expression in T regulatory cells in course of multiple sclerosis

J Neuroimmunol. 2010 Sep 14;226(1-2):165-71. doi: 10.1016/j.jneuroim.2010.06.009. Epub 2010 Jul 16.


Objectives: Multiple sclerosis (MS) is a chronic inflammatory response against constituents of the central nervous system. It is known that regulatory T cells (Tregs) play a key role in the autoimmune balance and their improper function may facilitate the expansion of autoaggressive T cell clones. Recently, microRNAs (miRNAs) have been involved in autoimmune disorders and their loss-of-function in immune cells was shown to facilitate systemic autoimmune disorders. Here, we analyzed the miRNA expression profile in Tregs from MS-RR.

Methods: We assessed miRNA genome-wide expression profile by microarray analysis on CD4(+)CD25(+high) T cells from 12 MS relapsing-remitting patients in stable condition and 14 healthy controls. Since CD4(+)CD25(+high) T cells comprise both T regulatory cells (CD4(+)CD25(+high)CD127(dim/-)) and T effector cells (CD4(+)CD25(+high)CD127(+)), we performed a quantitative RT-PCR on CD4(+)CD25(+high)CD127(dim/-) and CD4(+)CD25(+high)CD127(+) cells isolated from the same blood sample.

Results: We found 23 human miRNAs differentially expressed between CD4(+)CD25(high)bona fide Treg cells from MS patients vs. healthy donors, but, conversely, among the deregulated miRNAs, members of the miR-106b-25 were found down-regulated in MS patients when compared to healthy donors in CD4(+)CD25(high)CD127(dim/-) T regulatory cells. More interesting, the ratio between Treg/Teff showed an enrichment of these microRNA in T regulatory cells derived from patients if compared to healthy controls.

Conclusion: miR-106b and miR-25 were previously shown to modulate the TGF-β signaling pathway through their action on CDKN1A/p21 and BCL2L11/Bim. TGF-β is involved in T regulatory cells differentiation and maturation. Therefore, the deregulation of this miRNA cluster may alter Treg cells activity in course of MS, by altering TGF-β biological functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Coculture Techniques / methods
  • Female
  • Flow Cytometry / methods
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / immunology
  • Gene Expression Regulation / physiology*
  • Genome-Wide Association Study / methods
  • Humans
  • Lymphocyte Activation / immunology
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology*
  • Oligonucleotide Array Sequence Analysis / methods
  • T-Lymphocytes, Regulatory / classification
  • T-Lymphocytes, Regulatory / metabolism*
  • Transforming Growth Factor beta / metabolism


  • Antigens, CD
  • MicroRNAs
  • Transforming Growth Factor beta