The omega-3 fatty acid Docosahexaenoic acid overcomes the PKCζ deficiency in immature cord blood T cells and regulates maturation towards a Th1 cytokine bias
Presentation Time: -
Poster Board Number: B845
Abstract ID: 4441
Presenting Author:
Khalida Perveen , Research Assistant at SAiGENCI, Univ. of Adelaide, Women’s and Children’s Hospital
Abstract:
A significant number of babies born to women with a family history of allergy have transiently low levels of cord blood T cells (CBTC) PKCζ, and increased incidence of allergic sensitization by 2.5 y of age. Supplementing with ω-3 polyunsaturated fatty acids (PUFA) during pregnancy caused an increase in CBTC PKCζ levels and reduced the risk of atopic disease. The basis for the effects of PUFA remains poorly understood. Using a CBTC maturation culture model we demonstrate that this transient deficiency can be overcome by treating with ω-3 PUFA, docosahexaenoic acid (DHA) but not eicosapentaenoic acid. In contrast, the ω-6 PUFA, arachidonate (AA) decreased the PKCζ expression. Treatment of CBTC with DHA followed by maturation resulted in T (CD4+ and CD8+) cells producing decreased amounts of IL-4, increasing the IFN-γ: IL-4 ratio. In contrast, AA caused an IL-4 bias. The DHA-induced PKCζ increase was dependent on metabolism via the lipoxygenase pathways, and its metabolite Resolvin D1 was also effective. The AA metabolite 15d-prostaglandin J2, an activator of the Peroxisome Proliferator Activation Receptor γ, also caused a decrease in the levels of PKCζ, supported by the finding that the classical activator pioglitazone also decreased PKCζ expression. The results show that the ratio of ω-3 (DHA): ω-6 PUFA regulates the transition of the immature Th2 bias at birth to the mature Th1 cytokine propensity, providing avenues for early intervention to reduce the allergy risk.
The omega-3 fatty acid Docosahexaenoic acid overcomes the PKCζ deficiency in immature cord blood T cells and regulates maturation towards a Th1 cytokine bias
Category
Poster and Podium (Block Symposium)