GSE203460
Vitamin C enhances NF-?B-driven DNA demethylation and immunogenic properties of dendritic cells [RNA-Seq]
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 TNFß 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. 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