par Jebbawi, Fadi ;Fayyad Kazan, Hussein ;Merimi, Makram ;Lewalle, Philippe ;Verougstraete, Jean Christophe;Leo, Oberdan ;Romero, Pedro;Burny, Arsène ;Badran, Bassam ;Martiat, Philippe ;Rouas, Redouane
Référence Journal of translational medicine, 12, 1, 218
Publication Publié, 2014-08
Référence Journal of translational medicine, 12, 1, 218
Publication Publié, 2014-08
Article révisé par les pairs
Résumé : | Background: Recently, regulatory T (Treg) cells have gained interest in the fields of immunopathology, transplantation and oncoimmunology. Here, we investigated the microRNA expression profile of human natural CD8+CD25+ Treg cells and the impact of microRNAs on molecules associated with immune regulation.Methods: We purified human natural CD8+ Treg cells and assessed the expression of FOXP3 and CTLA-4 by flow cytometry. We have also tested the ex vivo suppressive capacity of these cells in mixed leukocyte reactions. Using TaqMan low-density arrays and microRNA qPCR for validation, we could identify a microRNA 'signature' for CD8+CD25+FOXP3+CTLA-4+ natural Treg cells. We used the 'TargetScan' and 'miRBase' bioinformatics programs to identify potential target sites for these microRNAs in the 3′-UTR of important Treg cell-associated genes.Results: The human CD8+CD25+ natural Treg cell microRNA signature includes 10 differentially expressed microRNAs. We demonstrated an impact of this signature on Treg cell biology by showing specific regulation of FOXP3, CTLA-4 and GARP gene expression by microRNA using site-directed mutagenesis and a dual-luciferase reporter assay. Furthermore, we used microRNA transduction experiments to demonstrate that these microRNAs impacted their target genes in human primary Treg cells ex vivo.Conclusions: We are examining the biological relevance of this 'signature' by studying its impact on other important Treg cell-associated genes. These efforts could result in a better understanding of the regulation of Treg cell function and might reveal new targets for immunotherapy in immune disorders and cancer. |