Zinc Modulates the Priming of T Helper 1, T Helper 17, and T Regulatory Cells in Allogeneic and in vitro Models

Introduction: Zinc is essential for the growth and differentiation of immune cells. Zinc insufficiency affects immune system function, thereby increasing infection susceptibility, autoimmunity, and allergies. Here, we aimed to determine the effects of zinc supplementation on T cell subpopulations, regulatory T (Tregs), T helper 1 (Th1), and T helper 17 (Th17) cells, in mixed lymphocyte cultures (MLC).Methods: Allogeneic immune reactions were imitative using mixed lymphocyte cultures, followed by incubation with zinc to further monitor their effects. Cells were analyzed by flow cytometry. Production of Interferon-gamma (IFN gamma), Interleukin-17 A (IL17A), and IL10 were analyzed by enzyme-linked immunosorbent assay. Th1 cell-specific Tbet, Th17 cell-specific RORC2, and Tregs-specific Foxp3 expression levels were determined by quantitative real-time PCR. Results: Zinc supplementation at a physiological dose significantly increased CD4+ Foxp3+ Tregs and CD25+ Foxp3+ Tregs numbers and slightly decreased CD4+ RORC2+ and CD25+ RORC2+ Th17 cell numbers. A significant reduction in IFN gamma production was observed in both restimulated T cells with autologous peripheral blood mononuclear cell (PBMC) and allogeneic PBMC compared to that in untreated T cells. Zinc significantly reduced IL17 expression, but the increase in IL10 expression was insignificant. In zinc-supplemented MLC, a non-significant decrease in Th1 or Th17 cell-specific transcription factors expression was observed, whereas there was a significant increase in Tregs-specific transcription factor expression. Conclusion: Zinc can stabilize Tregs participating in adverse immune reactions or in an in vitro transplantation model. Keywords: zinc, T helper 1, T helper 17, T regulatory, mixed lymphocyte culture