Intracellular free zinc up-regulates IFN-γ and T-bet essential for Th1 differentiation in Con-A stimulated HUT-78 cells

► Zinc deficiency impairs cell-mediated immunity in humans. ► We find zinc increases the expression of IL-2, IFN-γ, IL-12Rβ2, and T-bet, essential for Th1-cell differentiation in Th0 cells. ► Zinc-specific chelator, TPEN, decreases the mRNA expression of IFN-γ and T-bet in Con-A-stimulated cells. ► High level of zinc increases intracellular free zinc in Con-A-stimulated cells. ► We hypothesize that free zinc is a molecular signal involved in expression of cytokines and transcription factors.