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Status |
Public on Jan 22, 2014 |
Title |
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 |
Organism |
Homo sapiens |
Experiment type |
Non-coding RNA profiling by array
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Summary |
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).
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Overall design |
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).
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Contributor(s) |
Smigielska-Czepiel K, van den Berg A, Jellema P, van der Lei RJ, Bijzet J, Kluiver J, Boots AM, Brouwer E, Kroesen B |
Citation(s) |
24401767 |
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Submission date |
Sep 06, 2013 |
Last update date |
Jun 07, 2015 |
Contact name |
Bart-Jan Kroesen |
E-mail(s) |
b.j.kroesen@umcg.nl
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Phone |
+31 50 361 2937
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Organization name |
University of Groningen, University Medical Center Groningen
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Department |
Department of Laboratory Medicine
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Street address |
Hanzeplein 1
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City |
Groningen |
ZIP/Postal code |
9713GZ |
Country |
Netherlands |
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Platforms (1) |
GPL16770 |
Agilent-031181 Unrestricted_Human_miRNA_V16.0_Microarray (miRBase release 16.0 miRNA ID version) |
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Samples (32)
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GSM1225256 |
HC-2, Naive, Treg, Healthy control |
GSM1225257 |
HC-6b, Memory, Tconv, Healthy control |
GSM1225258 |
HC-6b, Memory, Treg, Healthy control |
GSM1225259 |
HC-6b, Naive, Tconv, Healthy control |
GSM1225260 |
HC-6b, Naive, Treg, Healthy control |
GSM1225261 |
RA-10, Memory, Tconv, New RA |
GSM1225262 |
RA-10, Memory, Treg, New RA |
GSM1225263 |
RA-10, Naive, Tconv, New RA |
GSM1225264 |
RA-10, Naive, Treg, New RA |
GSM1225265 |
RA-15, Memory, Tconv, 3 MTX |
GSM1225266 |
RA-15, Memory, Treg, 3 MTX |
GSM1225267 |
RA-15, Naive, Tconv, 3 MTX |
GSM1225268 |
RA-15, Naive, Treg, 3 MTX |
GSM1225269 |
RA-22, Memory, Tconv, 3 MTX |
GSM1225270 |
RA-22, Memory, Treg, 3 MTX |
GSM1225271 |
RA-22, Naive, Tconv, 3 MTX |
GSM1225272 |
RA-22, Naive, Treg, 3 MTX |
GSM1225273 |
RA-27, Memory, Tconv, New RA |
GSM1225274 |
RA-27, Memory, Treg, New RA |
GSM1225275 |
RA-27, Naive, Tconv, New RA |
GSM1225276 |
RA-27, Naive, Treg, New RA |
GSM1225277 |
RA-28, Memory, Tconv, MTX Ad |
GSM1225278 |
RA-28, Memory, Treg, MTX Ad |
GSM1225279 |
RA-28, Naive, Tconv, MTX Ad |
GSM1225280 |
RA-28, Naive, Treg, MTX Ad |
GSM1225281 |
RA-8, Memory, Tconv, MTX Ad |
GSM1225282 |
RA-8, Memory, Treg, MTX Ad |
GSM1225283 |
RA-8, Naive, Tconv, MTX Ad |
GSM1225284 |
RA-8, Naive, Treg, MTX Ad |
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Relations |
BioProject |
PRJNA218197 |
Supplementary file |
Size |
Download |
File type/resource |
GSE50646_RAW.tar |
93.9 Mb |
(http)(custom) |
TAR (of TXT) |
Processed data included within Sample table |
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