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

Giuseppe De Santis, Manuela Ferracin, Andrea Biondani, Luisa Caniatti, Maria Rosaria Tola, Massimiliano Castellazzi, Barbara Zagatti, Luca Battistini, Giovanna Borsellino, Enrico Fainardi, Riccardo Gavioli, Massimo Negrini, Roberto Furlan, Enrico Granieri

Research output: Contribution to journalArticlepeer-review

Abstract

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+highCD127dim/-) and T effector cells (CD4+CD25+highCD127+), we performed a quantitative RT-PCR on CD4+CD25+highCD127dim/- and CD4+CD25+highCD127+ cells isolated from the same blood sample. Results: We found 23 human miRNAs differentially expressed between CD4+CD25high 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+CD25highCD127dim/- 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.

Original languageEnglish
Pages (from-to)165-171
Number of pages7
JournalJournal of Neuroimmunology
Volume226
Issue number1-2
DOIs
Publication statusPublished - Sep 2010

Keywords

  • Autoimmunity
  • MicroRNA
  • Multiple sclerosis
  • T regulatory cell
  • TGF-beta

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology
  • Medicine(all)

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