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

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

来源：Journal of Neuroimmunology, 2010, 226(1-2): 165-171.

DOI：10.1016/j.jneuroim.2010.06.009

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

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 Tregfieff 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-beta signaling pathway through their action on CDKN1A/p21 and BCL2L11/Bim. TGF-beta 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-beta, biological functions.

• 出版日期2010-9-14