Polyunsaturated fatty acids regulate protein kinase C zeta levels in immature (cord blood) T cells, their maturation towards a Th1 cytokine bias and its significance in reducing allergy risk 3443

Abstract Description A significant number of babies born to women with a family history of allergy have transiently low levels of cord blood T cell protein kinase C (PKC)ζ, and increased incidence of allergic sensitisation by 2.5 y of age. We have provided compelling evidence for the role of PKCζ in regulating neonatal T cell development toward a Th1 cytokine propensity. We have now defined the transient deficient period after birth and show that interaction with nutrients during this period can increase and ‘normalise’ the PKCζ levels in immature T cells. In particular, we have demonstrated that polyunsaturated fatty acids are effective modulators of PKCζ levels. The results also identify which fatty acid structures are critical for achieving these changes and the fatty acid metabolic products responsible for their effects. These polyunsaturated fatty acids effects were reflected in the development of neonatal T cells from an immature allergy Th2 cytokine profile to a mature Th1 cytokine bias. The data identify a protein amenable to modulation by nutrients early after birth, representing a modification of the ‘hygiene hypothesis’ for preventing allergic sensitisation. Funding Sources Women’s and Children’s Research Foundation: Perveen_2025 Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)