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.[Figure not available: see fulltext.].