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

Détails

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Etat: Serval
Version: Final published version
ID Serval
serval:BIB_D16C5369C648
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A microRNA profile of human CD8(+) regulatory T cells and characterization of the effects of microRNAs on Treg cell-associated genes.
Périodique
Journal of translational medicine
Auteur(s)
Jebbawi F., Fayyad-Kazan H., Merimi M., Lewalle P., Verougstraete J.C., Leo O., Romero P., Burny A., Badran B., Martiat P., Rouas R.
ISSN
1479-5876 (Electronic)
ISSN-L
1479-5876
Statut éditorial
Publié
Date de publication
06/08/2014
Peer-reviewed
Oui
Volume
12
Pages
218
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural
Publication Status: epublish
Résumé
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.
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.
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.
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.

Mots-clé
3' Untranslated Regions/genetics, Antigens, CD/metabolism, CD8-Positive T-Lymphocytes/metabolism, CTLA-4 Antigen/metabolism, Cell Proliferation, Cell Separation, Forkhead Transcription Factors/genetics, Forkhead Transcription Factors/metabolism, Gene Expression Profiling, Gene Expression Regulation, HeLa Cells, Humans, Lentivirus/metabolism, Membrane Proteins/metabolism, MicroRNAs/genetics, MicroRNAs/metabolism, T-Lymphocytes, Regulatory/metabolism, Transcription, Genetic, Transduction, Genetic
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/09/2014 14:37
Dernière modification de la notice
09/05/2019 1:36
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