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

• Published in: Journal of neuroimmunology Vol. 226; no. 1; pp. 165 - 171
• Main Authors: De Santis, Giuseppe, Ferracin, Manuela, Biondani, Andrea, Caniatti, Luisa, Rosaria Tola, Maria, Castellazzi, Massimiliano, Zagatti, Barbara, Battistini, Luca, Borsellino, Giovanna, Fainardi, Enrico, Gavioli, Riccardo, Negrini, Massimo, Furlan, Roberto, Granieri, Enrico
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 14-09-2010
• Subjects: Adult; Allergy and Immunology; Analysis of Variance; Antigens, CD - genetics; Antigens, CD - metabolism; Autoimmune diseases; Autoimmunity; 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; MicroRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; Multiple sclerosis; Multiple Sclerosis - immunology; Multiple Sclerosis - pathology; Neurology; Oligonucleotide Array Sequence Analysis - methods; T regulatory cell; T-Lymphocytes, Regulatory - classification; T-Lymphocytes, Regulatory - metabolism; TGF-beta; Transforming Growth Factor beta - metabolism; Autoimmunity; Multiple sclerosis; T regulatory cell; TGF-beta; MicroRNA
• DOI: 10.1016/j.jneuroim.2010.06.009
• EISSN: 1872-8421
• ISSN: 0165-5728

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 + high CD127dim/− ) and T effector cells (CD4+ CD25 + high CD127+ ), we performed a quantitative RT-PCR on CD4+ CD25 + high CD127dim/− and CD4+ CD25 + high CD127+ 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+ CD25high CD127dim/− 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.