|
|
GEO help: Mouse over screen elements for information. |
|
Status |
Public on Dec 15, 2016 |
Title |
Whole-genome expression profiles of CD4+ CD28+ and CD4+ CD28null T lymphocytes. |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
|
Summary |
The loss of the CD28 co-stimulatory molecule by CD4+ lymphocytes (CD28null T cells) is accompanied by the acquisition of new biological and functional properties that lead to an impaired immune response. The regulatory mechanisms that govern the appearance and function of this cell subset in several inflammatory disorders and in healthy individuals, mainly in aging, are yet a controversial point. Here, we provide the whole-genome DNA methylation and gene expression profiles of CD28null T cells and its CD28+ counterpart. A comparative analysis reveals that 296 genes are differentially methylated between both cell subsets. One hundred sixty (160 genes) associated with the cytotoxicy ability (e.g., GRZB, TYROBP, and RUNX3) and cytokine/chemokine signaling (e.g., CX3CR1, CD27, and IL1R) are demetylated in CD28null T cells, whilst 136 de-novo methylated genes matched with defects in the TCR signaling pathway (e.g., ITK, TXK, CD3G, and LCK). Moreover, we show that genes related inflammasome activation are differentially expressed between CD28null and CD28+ T cells, highlight the contribution of this pathways to the pro-inflammatory profile of CD28null T cells. Overall, our results reveal that CD28null T cells have a unique DNA methylation landscape, which is associated with alteration in gene expression and contributes to the functionality of these cells. Understanding these epigenetic regulatory mechanisms could provide novel therapeutic strategies to prevent the accumulation and activation of these cells in aging and inflammatory disorders.
|
|
|
Overall design |
Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation from 24 healthy donors. Further, CD4+CD28null and CD4+CD28+ T lymphocytes were purified using CD4 Multisort kit and CD28 MicroBead kit (Miltenyi Biotec) following the manufacturer´s instructions or sorted with a BD FACSARIA II cytometer (BD Bioscience) after staining with CD4-APC and CD28-FITC monoclonal antibodies (mAbs) (BioLegend). Purity was always higher than 95% for all samples. Datasets were generated from two biological replicates per each cell type (CD28null and CD28+) obtained from a pool of twelve healthy donors each one. Samples were pooled using the same RNA quantity by donor. For expression data, a gene was considered to be differentially expressed if had a value of FDR-adjusted p < 0.05 and at least an expression of >1.5 fold-change (FC).
|
|
|
Contributor(s) |
Suarez-Alvarez B, Rodriguez RM, Schlangen K, Raneros AB, Márquez L, Fernandez AF, Díaz-Corte C, Aransay AM, López-Larrea C |
Citation missing |
Has this study been published? Please login to update or notify GEO. |
Submission date |
Mar 07, 2016 |
Last update date |
Aug 16, 2018 |
Contact name |
Beatriz Suarez-Alvarez |
E-mail(s) |
beatriz.suarez@fjd.es, bea230@hotmail.com
|
Phone |
+34600219045
|
Organization name |
Hospital Universitario Central de Asturias
|
Lab |
Immunology Department
|
Street address |
Celestino Villamil s/n
|
City |
Oviedo |
State/province |
Oviedo |
ZIP/Postal code |
33006 |
Country |
Spain |
|
|
Platforms (1) |
GPL6947 |
Illumina HumanHT-12 V3.0 expression beadchip |
|
Samples (4)
|
|
This SubSeries is part of SuperSeries: |
GSE78942 |
Whole-genome DNA methylation and expression profiles of CD4+ CD28+ and CD4+ CD28null T lymphocytes |
|
Relations |
BioProject |
PRJNA314476 |
Supplementary file |
Size |
Download |
File type/resource |
GSE78941_RAW.tar |
6.2 Mb |
(http)(custom) |
TAR |
GSE78941_non_normalized.txt.gz |
1.5 Mb |
(ftp)(http) |
TXT |
Processed data included within Sample table |
|
|
|
|
|