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| Status |
Public on Oct 06, 2022 |
| Title |
Vitamin C enhances NF-?B-driven DNA demethylation and immunogenic properties of dendritic cells [methylation I] |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
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| Summary |
Dendritic cells (DCs) are central in immune responses, bridging the adaptive and innate systems. The study of the in vitro differentiation of DCs from monocytes provides both an in-depth understanding of the analogous in vivo process and a potential source for cancer cell therapy. Active DNA demethylation has been previously reported to be crucial in DC differentiation. Vitamin C, an essential nutrient, is a known cofactor of ten-eleven translocation (TET) enzymes, which drive active demethylation. Currently, the effects of vitamin C treatment on human immune cells are poorly understood. In this study, we have analyzed the epigenomic and transcriptomic reprogramming orchestrated by vitamin C in monocyte-derived DC differentiation and maturation. We have detected extensive demethylation produced by vitamin C treatment, together with concordant gene expression changes during DC maturation. p65, a component of NF-kB, interacts with TET2 and produces both vitamin C-mediated gene upregulation and DNA demethylation during DC maturation, as demonstrated by chemical inhibition. Moreover, vitamin C increases TNFβ production in DCs through p65, in concordance with the upregulation of its coding gene and DNA demethylation of adjacent CpGs. Finally, vitamin C increases DC's ability to stimulate the proliferation of autologous antigen-specific T cells. This work provides a potential strategy for the improvement of cell therapies based on monocyte-derived DCs, as well as a feasible mechanism of action for intravenous high-dose vitamin C treatment in patients.
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| Overall design |
Monocytes were differentiated to Dcs in the presence/absence of vitamin C. DCs were maturated with LPS. Three biological replicates are included and three different conditions: monocytes, DC_d2, DC_d2vitC, iDCs, iDCvitC, mDCs, and, mDCvitC
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| Contributor(s) |
Morante-Palacios O, Godoy-Tena G, Calafell-Segura J, Ciudad L, Martínez-Cáceres EM, Sardina J, Ballestar E |
| Citation(s) |
36305821 |
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| Submission date |
May 20, 2022 |
| Last update date |
Nov 29, 2022 |
| Contact name |
Esteban Ballestar |
| Organization name |
Josep Carreras Research Institute (IJC)
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| Lab |
Epigenetics and Immune Disease
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| Street address |
Ctra de Can Ruti, Camí de les Escoles s/n
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| City |
Badalona, Barcelona |
| State/province |
N/A = Not Applicable |
| ZIP/Postal code |
08916 |
| Country |
Spain |
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| Platforms (1) |
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| Samples (28)
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| This SubSeries is part of SuperSeries: |
| GSE203463 |
Vitamin C enhances NF-κB-driven DNA demethylation and immunogenic properties of dendritic cells |
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| Relations |
| BioProject |
PRJNA840903 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE203461_RAW.tar |
561.8 Mb |
(http)(custom) |
TAR (of IDAT) |
| GSE203461_matrix.normalized.bvalues.txt.gz |
207.1 Mb |
(ftp)(http) |
TXT |
| GSE203461_matrix.raw.signal.txt.gz |
160.5 Mb |
(ftp)(http) |
TXT |
| Processed data are available on Series record |
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