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European Journal of Nutrition

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01-08-2017 | Original Contribution

Zinc supplementation induces CD4⁺CD25⁺Foxp3⁺ antigen-specific regulatory T cells and suppresses IFN-γ production by upregulation of Foxp3 and KLF-10 and downregulation of IRF-1

Authors: Martina Maywald, Lothar Rink

Published in: European Journal of Nutrition | Issue 5/2017

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 [³H]-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 CD4⁺CD25⁺Foxp3⁺ and CD4⁺CD25⁺CTLA-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.

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Title: Zinc supplementation induces CD4+CD25+Foxp3+ antigen-specific regulatory T cells and suppresses IFN-γ production by upregulation of Foxp3 and KLF-10 and downregulation of IRF-1
Authors: Martina Maywald
Lothar Rink
Publication date: 01-08-2017
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nutrition / Issue 5/2017
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-016-1228-7

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Abstract

Purpose

Methods

Results

Conclusion

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