Vitamin C enhances NF-κB-driven epigenomic reprogramming and boosts the immunogenic properties of dendritic cells
Morante-Palacios, Octavio (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Godoy-Tena, Gerard (Ludwig-Maximilians-Universität München)
Calafell-Segura, Josep (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Ciudad, Laura (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Martínez-Cáceres, Eva M. (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Sardina, José Luis (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ballestar, Esteban (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Universitat Autònoma de Barcelona

Fecha:	2022
Resumen:	Dendritic cells (DCs), the most potent antigen-presenting cells, are necessary for effective activation of naïve 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-κB/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 TNFβ production in DCs through NF-κB, 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.
Ayudas:	Agencia Estatal de Investigación PID2020-117212RB-I00 Ministerio de Ciencia, Innovación y Universidades PID2019-111243RA-I00
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Nucleic acids research, Vol. 50 (october 2022) , p. 10981-10994, ISSN 1362-4962

DOI: 10.1093/nar/gkac941
PMID: 36305821

14 p, 3.5 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Instituto de Investigación contra la Leucemia Josep Carreras
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