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| Status |
Public on Dec 15, 2016 |
| Title |
Whole-genome DNA methylation profiles of CD4+ CD28+ and CD4+ CD28null T lymphocytes. |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
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| 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 profile 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). 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.
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| 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 DNA quantity by donor. Bisulphite converted DNA from the two pools were hybridised to the Illumina Infinium 27k Human Methylation Beadchip.
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| 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 |
Dec 16, 2016 |
| Contact name |
Beatriz Suarez-Alvarez |
| E-mail(s) |
beatriz.suarez@fjd.es, bea230@hotmail.com
|
| Phone |
+34600219045
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| Organization name |
Hospital Universitario Central de Asturias
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| Lab |
Immunology Department
|
| Street address |
Celestino Villamil s/n
|
| City |
Oviedo |
| State/province |
Oviedo |
| ZIP/Postal code |
33006 |
| Country |
Spain |
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| Platforms (1) |
| GPL8490 |
Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2) |
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| Samples (4)
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| GSM2081537 |
CD4+CD28null T cells pool1 [methylation] |
| GSM2081538 |
CD4+CD28null T cells pool2 [methylation] |
| GSM2081539 |
CD4+CD28+ T cells pool1 [methylation] |
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| This SubSeries is part of SuperSeries: |
| GSE78942 |
Whole-genome DNA methylation and expression profiles of CD4+ CD28+ and CD4+ CD28null T lymphocytes |
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| Relations |
| BioProject |
PRJNA314477 |
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