A microRNA profile of human CD8+ regulatory T cells and characterization of the effects of microRNAs on Treg cell-associated genes
| Autor: | Redouane Rouas, Oberdan Leo, Philippe Martiat, Bassam Badran, Jean-Christophe Verougstraete, Philippe Lewalle, Pedro Romero, Arsène Burny, Fadi Jebbawi, Makram Merimi, Hussein Fayyad-Kazan |
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| Jazyk: | angličtina |
| Předmět: |
Transcription
Genetic FOXP3 chemical and pharmacologic phenomena Cell Separation Biology CD8-Positive T-Lymphocytes T-Lymphocytes Regulatory General Biochemistry Genetics and Molecular Biology MiRBase GARP Antigens CD Transduction Genetic microRNA Humans CTLA-4 Antigen 3' Untranslated Regions Cell Proliferation Regulation of gene expression Medicine(all) Biochemistry Genetics and Molecular Biology(all) Research Gene Expression Profiling 3' Untranslated Regions/genetics Antigens CD/metabolism CD8-Positive T-Lymphocytes/metabolism CTLA-4 Antigen/metabolism Forkhead Transcription Factors/genetics Forkhead Transcription Factors/metabolism Gene Expression Regulation HeLa Cells Lentivirus/metabolism Membrane Proteins/metabolism MicroRNAs/genetics MicroRNAs/metabolism T-Lymphocytes Regulatory/metabolism Lentivirus Membrane Proteins Forkhead Transcription Factors hemic and immune systems General Medicine MicroRNA Expression Profile CD8 Regulatory T cells Sciences bio-médicales et agricoles 3. Good health Cell biology Transplantation Gene expression profiling MicroRNAs CTLA-4 Immunology Biologie |
| Zdroj: | Journal of translational medicine, vol. 12, pp. 218 Journal of translational medicine, 12 (1 Journal of Translational Medicine |
| ISSN: | 1479-5876 |
| DOI: | 10.1186/s12967-014-0218-x |
| Popis: | 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. SCOPUS: ar.j info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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