A microRNA profile of human CD8+ regulatory T cells and characterization of the effects of microRNAs on Treg cell-associated genes

Journal of Translational Medicine

Redouane Rouas²  Philippe Martiat²  Bassam Badran¹  Arsene Burny²  Pedro Romero⁴  Oberdan Leo²  Jean-Christophe Verougstraete³  Philippe Lewalle²  Makram Merimi²  Hussein Fayyad-Kazan²  Fadi Jebbawi² 

[1] Department of Biochemistry, Laboratory of Immunology, EDST-PRASE, Faculty of Sciences, Lebanese University, Hadath-Beirut, Lebanon;Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, 121, Boulevard de Waterloo, Bruxelles, 1000, Belgium;Department of Gynecology and Obstetrics, Clinique Saint-Pierre, Ottignies, Belgium;Ludwig Center for Cancer Research of the University of Lausanne, Lausanne, Switzerland

关键词: CD8;    GARP;    CTLA-4;    FOXP3;    microRNA;    Regulatory T cells;   

Others  :  1148585
DOI  :  10.1186/s12967-014-0218-x

 received in 2014-03-09, accepted in 2014-07-21,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Jebbawi et al.; licensee BioMed Central Ltd.

【 图 表 】

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