PMID- 36305821
OWN - NLM
STAT- MEDLINE
DCOM- 20221109
LR  - 20221110
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 50
IP  - 19
DP  - 2022 Oct 28
TI  - Vitamin C enhances NF-kappaB-driven epigenomic reprogramming and boosts the 
      immunogenic properties of dendritic cells.
PG  - 10981-10994
LID - 10.1093/nar/gkac941 [doi]
AB  - Dendritic cells (DCs), the most potent antigen-presenting cells, are necessary 
      for effective activation of naive T cells. DCs' immunological properties are 
      modulated in response to various stimuli. Active DNA demethylation is crucial for 
      DC differentiation and function. Vitamin C, a known cofactor of ten-eleven 
      translocation (TET) enzymes, drives active demethylation. Vitamin C has recently 
      emerged as a promising adjuvant for several types of cancer; however, its effects 
      on human immune cells are poorly understood. In this study, we investigate the 
      epigenomic and transcriptomic reprogramming orchestrated by vitamin C in 
      monocyte-derived DC differentiation and maturation. Vitamin C triggers extensive 
      demethylation at NF-kappaB/p65 binding sites, together with concordant upregulation 
      of antigen-presentation and immune response-related genes during DC maturation. 
      p65 interacts with TET2 and mediates the aforementioned vitamin C-mediated 
      changes, as demonstrated by pharmacological inhibition. Moreover, vitamin C 
      increases TNFbeta production in DCs through NF-kappaB, in concordance with the 
      upregulation of its coding gene and the demethylation of adjacent CpGs. Finally, 
      vitamin C enhances DC's ability to stimulate the proliferation of autologous 
      antigen-specific T cells. We propose that vitamin C could potentially improve 
      monocyte-derived DC-based cell therapies.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic 
      Acids Research.
FAU - Morante-Palacios, Octavio
AU  - Morante-Palacios O
AD  - Epigenetics and Immune Disease Group, Josep Carreras Research Institute 
      (IJC), 08916, Badalona, Barcelona, Spain.
AD  - Germans Trias i Pujol Research Institute (IGTP), 08916, Badalona, Barcelona, 
      Spain.
FAU - Godoy-Tena, Gerard
AU  - Godoy-Tena G
AD  - Epigenetics and Immune Disease Group, Josep Carreras Research Institute 
      (IJC), 08916, Badalona, Barcelona, Spain.
FAU - Calafell-Segura, Josep
AU  - Calafell-Segura J
AD  - Epigenetics and Immune Disease Group, Josep Carreras Research Institute 
      (IJC), 08916, Badalona, Barcelona, Spain.
FAU - Ciudad, Laura
AU  - Ciudad L
AD  - Epigenetics and Immune Disease Group, Josep Carreras Research Institute 
      (IJC), 08916, Badalona, Barcelona, Spain.
FAU - Martinez-Caceres, Eva M
AU  - Martinez-Caceres EM
AD  - Division of Immunology, Germans Trias i Pujol Hospital, LCMN, Germans Trias 
      iPujol Research Institute (IGTP), 08916, Badalona, Barcelona, Spain.
AD  - Department of Cell Biology, Physiology, Immunology, Autonomous University of 
      Barcelona, 08193, Bellaterra, Barcelona, Spain.
FAU - Sardina, Jose Luis
AU  - Sardina JL
AD  - Epigenetic Control of Haematopoiesis Group, Josep Carreras Research Institute 
      (IJC), 08916, Badalona, Barcelona, Spain.
FAU - Ballestar, Esteban
AU  - Ballestar E
AUID- ORCID: 0000-0002-1400-2440
AD  - Epigenetics and Immune Disease Group, Josep Carreras Research Institute 
      (IJC), 08916, Badalona, Barcelona, Spain.
AD  - Germans Trias i Pujol Research Institute (IGTP), 08916, Badalona, Barcelona, 
      Spain.
AD  - Epigenetics in Inflammatory and Metabolic Diseases Laboratory, Health Science 
      Center (HSC), East China Normal University (ECNU), Shanghai 200241, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - PQ6CK8PD0R (Ascorbic Acid)
RN  - 0 (NF-kappa B)
RN  - 0 (RELA protein, human)
RN  - EC 1.13.11.- (TET2 protein, human)
SB  - IM
MH  - Humans
MH  - *Ascorbic Acid/pharmacology
MH  - Cell Differentiation/genetics
MH  - *Dendritic Cells
MH  - *NF-kappa B/metabolism
MH  - T-Lymphocytes/metabolism
MH  - *Epigenesis, Genetic
MH  - Cellular Reprogramming
PMC - PMC9638940
EDAT- 2022/10/29 06:00
MHDA- 2022/11/09 06:00
PMCR- 2022/10/28
CRDT- 2022/10/28 10:43
PHST- 2022/10/10 00:00 [accepted]
PHST- 2022/09/23 00:00 [revised]
PHST- 2022/06/22 00:00 [received]
PHST- 2022/10/29 06:00 [pubmed]
PHST- 2022/11/09 06:00 [medline]
PHST- 2022/10/28 10:43 [entrez]
PHST- 2022/10/28 00:00 [pmc-release]
AID - 6777795 [pii]
AID - gkac941 [pii]
AID - 10.1093/nar/gkac941 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2022 Oct 28;50(19):10981-10994. doi: 10.1093/nar/gkac941.