While immunodeficiency of immaturity of the neonate has been considered important as the basis for unusual susceptibility to infection, it has also been recognized that the ability to progress from an immature Th2 cytokine predominance to a Th1 profile has relevance in determining whether children will develop allergy, providing an opportunity for epigenetic regulation through environmental pressures. However, this notion remains relatively unexplored. Here, we present evidence that there are two major control points to explain the immunodeficiency in cord blood (CB) T-cells, a deficiency in interleukin (IL)-12 (IL-12) producing and IL-10 overproducing accessory cells, leading to a decreased interferon ã (IFNã) synthesis and the other, an intrinsic defect in T-cell protein kinase C (PKC) æ (PKCæ) expression. An important finding was that human CB T-cells rendered deficient in PKCæ, by shRNA knockdown, develop into low tumour necrosis factor á (TNFá) and IFNã but increased IL-13 producing cells. Interestingly, we found that the increase in PKCæ levels in CB T-cells caused by prenatal supplementation with fish oil correlated with modifications of histone acetylation at the PKCæ gene (PRKCZ) promoter. The data demonstrate that PKCæ expression regulates the maturation of neonatal T-cells into specific functional phenotypes and that environmental influences may work via PKCæ to regulate these phenotypes and disease susceptibility.
Acetylation Analysis of Variance