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

ObjectivesMultiple 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.MethodsWe 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.ResultsWe found 23 human miRNAs differentially expressed between CD4+CD25highbona 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.ConclusionmiR-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.