Protein kinase Cζ: A novel protective neonatal T-cell marker that can be upregulated by allergy prevention strategies

Abstract

Background: Variations in neonatal T-cell function have been associated with allergic disease. Objectives: To examine the relationship between neonatal T-cell protein kinase (PKC) expression and subsequent allergic disease. Methods: T cells were purified from cord blood samples (n = 74) obtained from a cohort of mothers who received either 4 g/d fish oil or a placebo from 20 weeks of gestation. PKC expression was examined in relationship to supplementation, fatty acid levels, cytokine production, and allergic outcomes at 1 year and 2.5 years of age. Results: Neonatal T-cell PKCζ expression was lower in children who had evidence of allergic disease at 1 year (P = .001) and 2.5 years (P = .052) of age. It was also lower in children with sensitization (positive skin prick test) at each age (P = .02 and P = .072, respectively). PKCζ expression was inversely correlated to PKCα (r = −0.28; P = .025), which was strongly related to IL-5 responses to allergens (ovalbumin, r = 0.59; P = .003; dust mite, r = 0.52; P = .011) at 1 year of age. Fish oil supplementation was associated with significantly higher PKCζ expression (P = .014), whereas most other isozymes were reduced by fish oil supplementation. Conclusion: This is the first study to show that allergic disease is associated with altered expression of T-cell PKC isozymes in the neonatal period. It has also demonstrated that fish oil can modulate expression of PKC isozymes in a potentially favorable direction. Clinical implications: Protein kinase Cζ should be explored further as an early marker and potential target for disease prevention.