Diuron modulates the DNA methylation status of the ILT7 and TRAIL/TNFSF10 genes and decreases the killing activity of plasmacytoid dendritic cells

Abstract

Background: Plasmacytoid dendritic cell (pDC) is described as the Swiss knife of immune system. Thus, the understanding of aberrant epigenetic reprogramming of genes governing the pDC functionality by pollutants appears such as an attractive research point. Results: Our study has investigated the effect of Diuron (an herbicide) on the pDC-killing activity towards cancer cells. Thus, we observed that the Diuron exposure of pDC promotes a context of global DNA hypomethylation, which is associated with a phenotype of decrease of the killing activity of pDC towards cancer cells. At molecular level, our data associated the Diuron-induced global DNA hypomethylation with the elevated expression of TET2, an epigenetic player involved in DNA demethylation processes, and the decrease of the pDC-killing activity with the decrease of TRAIL expression and the increase of ILT7 expression. Conclusions: Thus, our article reports that a pollutant (Diuron) induces an epigenetic reprogramming of a subtype of immune cell (pDC), which decreases its killing activity towards tumors cells. In some context, this mechanism might be conducive to the initiation of pathologies.

Modulation of DNA Methylation/Demethylation Reactions Induced by Nutraceuticals and Pollutants of Exposome Can Promote a C > T Mutation in the Breast Cancer Predisposing Gene PALB2

“…Our second hypothesis is based on the idea of using exposome compounds to guide the DNA demethylation reaction toward 5 mC deamination while blocking the action of the TDG enzyme, that is, the enzyme that initiates T/G mismatch repair ( Figure 1 ). To investigate this hypothesis, we used Diuron and PFOA as two exposome compounds since these both compounds are already known or suspected to modulate DNA methylation levels [ 23 , 35 , 36 ] ( Figure 2 ). About our working dose, we used concentration ranges based on the consideration of the maximum allowable concentrations (MAC) of these both compounds [ 37 , 38 ].…”

Adenosine Methylation Level of miR-125a-5p Promotes Anti-PD-1 Therapy Escape through the Regulation of IGSF11/VSIG3 Expression

“…In this assay, the lysis of H1975 cells is determined by labeling these cells with fluorescent molecules, co-incubating them with IL2-activated PBMC, then measuring the release of the labeled molecule in the supernatant. DELFIA EuTDA Cell Cytotoxicity (#AD0116, Perkin Elmer, Villebon-sur-Yvette, France) reagents were used as previously described (Briand et al 2019) [21]. For PBMC isolation, whole blood was diluted with an equal amount of 1× phosphate-buffered saline (PBS) and placed on top of Ficoll-Paque PLUS (#17-1440-02, VWR, Rosny-sous-Bois, France) in tubes for centrifugation at room temperature for 20 min at 1000× g. PBMCs were next carefully collected from the interface layer between the blood plasma and Ficoll solution.…”