Identification of a Human Natural Regulatory T Cell Micro-RNA Signature and Demonstration of the Major Role Played by miR31 in the Control of Foxp3 Expression

Regulatory T cells are the main mediators of dominant tolerance. Their mechanisms of action and applications are subjects of considerable debate at the moment. However, a micro-RNA human Treg signature has not been described yet. We investigated human natural regulatory T-cells derived from cord blood and identified, using TLDA and qPCR, a signature composed of five micro-RNAs (21, 31, 125a, 181c and 374). Among those five, two were considerably under-expressed (miR31 and miR125a). We identified a functional binding site for miR31 in the 3′ UTR of the Foxp3 mRNA. We show that Foxp3 gene expression can be directly regulated by miR31. However, our experiments demonstrate that two distinct mechanisms must cooperate to regulate play the global level of expression of FoxP3, one mediated via miR31, and the second one at the promoter site of the gene. This part of the work is still in progress. In conclusion, not only have we found and validated a miR signature for human natural Treg, but we also unveiled some of the mechanisms by which this signature was related to the control of the Foxp3 protein levels in these cells.