DNA methylation mediates the effect of exposure to prenatal maternal stress on cytokine production in children at age 13½ years: Project Ice Storm

Prenatal maternal stress (PNMS) is an important programming factor of postnatal immunity. We tested here the hypothesis that DNA methylation of genes in the NF-κB signaling pathway in T cells mediates the effect of

The present study provides preliminary evidence supporting the mediating role of DNA methylation in the association between objective aspects of PNMS and child immune states, favoring a Th2 shift.

Bootstrapping analyses were performed with 47 CpGs across a selection of 20 genes for Th1-type cytokines (IFN-γ and IL-2) and Th2-type cytokines (IL-4 and IL-13). Six CpGs in six different NF-κB signaling genes (PIK3CD, PIK3R2, NFKBIA, TRAF5, TNFRSF1B, and LTBR) remained as significant negative mediators of objective PNMS on IFN-γ secretion after correcting for multiple comparisons. However, no mediation effects on IL-2, IL-4 and IL-13 survived Bonferroni correction. Conclusions: The present study provides preliminary evidence supporting the mediating role of DNA methylation in the association between objective aspects of PNMS and child immune states, favoring a Th2 shift.