Transcriptomics

Dataset Information

4

Comprehensive analysis of miRNA expression in T-cell subsets of Rheumatoid arthritis patients and healthy controls reveals defined miRNA signatures of naive and memory Tregs


ABSTRACT: Disturbed expression of microRNAs (miRNAs) in regulatory T-cells (Tregs) leads to development of autoimmunity in experimental mouse models. However, the miRNA expression signature characterizing Tregs of autoimmune diseases, such as rheumatoid arthritis (RA) has not been determined yet. Moreover, the technical limitations prevented the analysis of such minute T-cell population as naive and memory Tregs. In this study we have used a microarray approach to comprehensively analyze miRNA expression signatures of naive Tregs (CD4+CD45RO-CD25++), memory Tregs (CD4+CD45RO+CD25+++), as well as conventional naive (CD4+CD45RO-CD25-) and memory (CD4+CD45RO+CD25-) T-cells (Tconvs) derived from peripheral blood of RA patients, and matched healthy controls. Differential expression of selected miRNAs was validated by TaqMan-based qRT-PCR. We found a positive correlation between increased expression of miR-451 in T-cells of RA patients and disease activity score (DAS28), ESR levels, and serum levels of IL-6. Moreover, we found characteristic, disease and treatment independent, global miRNA expression signatures defining naive Tregs, memory Tregs, naive Tconvs and memory Tconvs. The analysis allowed us to define miRNAs characteristic for a general naive phenotype (e.g. miR-92a), a general memory phenotype (e.g. miR-21, miR-155), and most importantly miRNAs specifically expressed in both naive and memory Tregs, defining as such the Treg phenotype (i.e. miR-146a, miR-3162, miR-1202, miR-1246a, and miR-4281). MicroRNA profiling was performed in four CD4+ T-cell subsets: naive Tconventional (CD3+CD8-CD45RO-CD25-), naive Tregulatory (CD3+CD8-CD45RO-CD25+), memory Tconventional (CD3+CD8-CD45RO+CD25-), and memory Tregulatory (CD3+CD8-CD45RO+CD25+) derived from 2 healthy controls, and 6 rheumatoid arthritis patients (total n=8).

ORGANISM(S): Homo sapiens  

SUBMITTER: Elisabeth Brouwer   Bart-Jan Kroesen  Anne M Boots  Pytrick Jellema  Katarzyna Smigielska-Czepiel  Roelof J van der Lei  Anke van den Berg  Joost Kluiver  Johan Bijzet 

PROVIDER: E-GEOD-50646 | ArrayExpress | 2014-01-22

SECONDARY ACCESSION(S): GSE50646PRJNA218197

REPOSITORIES: GEO, ArrayExpress

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Publications

Comprehensive analysis of miRNA expression in T-cell subsets of rheumatoid arthritis patients reveals defined signatures of naive and memory Tregs.

Smigielska-Czepiel K K   van den Berg A A   Jellema P P   van der Lei R J RJ   Bijzet J J   Kluiver J J   Boots A M H AM   Brouwer E E   Kroesen B-J BJ  

Genes and immunity 20140109 2


Disturbed expression of microRNAs (miRNAs) in regulatory T cells (Tregs) leads to development of autoimmunity in experimental mouse models. However, the miRNA expression signature characterizing Tregs of autoimmune diseases, such as rheumatoid arthritis (RA) has not been determined yet. In this study, we have used a microarray approach to comprehensively analyze miRNA expression signatures of both naive Tregs (CD4+CD45RO-CD25++) and memory Tregs (CD4+CD45RO+CD25+++), as well as conventional naiv  ...[more]

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