We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Zinc supplementation induces CD4CD25Foxp3 antigen-specific regulatory T cells and suppresses IFN-γ production by upregulation of Foxp3 and KLF-10 and downregulation of IRF-1.
- Authors
Maywald, Martina; Rink, Lothar
- Abstract
Purpose: The essential trace element zinc plays a fundamental role in immune function and regulation since its deficiency is associated with autoimmunity, allergies, and transplant rejection. Thus, we investigated the influence of zinc supplementation on the Th1-driven alloreaction in mixed lymphocyte cultures (MLC), on generation of antigen-specific T cells, and analyzed underlying molecular mechanisms. Methods: Cell proliferation and pro-inflammatory cytokine production were monitored by [H]-thymidine proliferation assay and ELISA, respectively. Analysis of surface and intracellular T cell marker was performed by flow cytometry. Western blotting and mRNA analysis were used for Foxp3, KLF-10, and IRF-1 expression. Results: Zinc supplementation on antigen-specific T cells in physiological doses (50 µM) provokes a significant amelioration of cell proliferation and pro-inflammatory cytokine production after reactivation compared to untreated controls. Zinc administration on MLC results in an increased induction and stabilization of CD4CD25Foxp3 and CD4CD25CTLA-4 T cells ( p < 0.05). The effect is based on zinc-induced upregulation of Foxp3 and KLF-10 and downregulation of IRF-1. However, in resting lymphocytes zinc increases IRF-1. Conclusion: In summary, zinc is capable of ameliorating the allogeneic immune reaction by enhancement of antigen-specific iTreg cells due to modulation of essential molecular targets: Foxp3, KLF-10, and IRF-1. Thus, zinc can be seen as an auspicious tool for inducing tolerance in adverse immune reactions.
- Subjects
IMMUNE system physiology; CELL proliferation; ANTIGENS; BIOLOGICAL models; CYTOKINES; ENZYME-linked immunosorbent assay; FLOW cytometry; LYMPHOCYTES; PROBABILITY theory; T cells; WESTERN immunoblotting; ZINC; STATISTICAL significance; IN vitro studies
- Publication
European Journal of Nutrition, 2017, Vol 56, Issue 5, p1859
- ISSN
1436-6207
- Publication type
Article
- DOI
10.1007/s00394-016-1228-7