The role of PKCζ in cord blood T-cell maturation towards Th1 cytokine profile and its epigenetic regulation by fish oil

Hani Harb, James Irvine, Manori Amarasekera, Charles S. Hii, Dörthe A. Kesper, Yue Fang Ma, Nina D'Vaz, Harald Renz, Daniel P. Potaczek, Susan L. Prescott, Antonio Ferrante

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    13 Citations (Scopus)

    Abstract

    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 γ (IFNγ) synthesis and the other, an intrinsic defect in T-cell protein kinase C (PKC) ζ (PKCζ) expression. An important finding was that human CB T-cells rendered deficient in PKCζ, by shRNA knockdown, develop into low tumour necrosis factor α (TNFα) and IFNγ but increased IL-13 producing cells. Interestingly, we found that the increase in PKCζ levels in CB T-cells caused by prenatal supplementation with fish oil correlated with modifications of histone acetylation at the PKCζ gene (PRKCZ) promoter. The data demonstrate that PKCζ expression regulates thematuration of neonatal T-cells into specific functional phenotypes and that environmental influences may work via PKCζ to regulate these phenotypes and disease susceptibility.

    Original languageEnglish
    Article numberBSR2016048
    JournalBioscience Reports: molecular and cellular biology of the cell surface
    Volume37
    Issue number2
    DOIs
    Publication statusPublished - 28 Apr 2017

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  • Cite this

    Harb, H., Irvine, J., Amarasekera, M., Hii, C. S., Kesper, D. A., Ma, Y. F., D'Vaz, N., Renz, H., Potaczek, D. P., Prescott, S. L., & Ferrante, A. (2017). The role of PKCζ in cord blood T-cell maturation towards Th1 cytokine profile and its epigenetic regulation by fish oil. Bioscience Reports: molecular and cellular biology of the cell surface, 37(2), [BSR2016048]. https://doi.org/10.1042/BSR20160485