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Zinc enhances the number of regulatory T cells in allergen-stimulated cells from atopic subjects

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Abstract

Purpose

The trace element zinc is essential for immune function and its regulation. Since zinc deficiency and allergic hyperresponsive reactions are often accompanied, the influence of zinc on allergen-induced cell growth, CD4+ regulatory T (Treg) cell numbers and cytokine expression during allergic immune reactions was investigated.

Methods

Peripheral blood mononuclear cells (PBMCs) from non-atopic and atopic subjects were treated with timothy grass allergen pre-incubated with or without zinc. Proliferation was determined by analyzing the incorporation of 3H-thymidine. Intracellular zinc and Foxp3 levels and cell surface antigens were measured by FACS, cytokine expression by ELISA and real-time PCR.

Results

Incubation with 50 μM zinc sulfate (Zn50) enhances cytosolic zinc concentrations in CD3+ T cells. The data also reveal that the combination of Zn50 plus allergen significantly reduces PBMC proliferation of atopic subjects. Additionally, Zn50 plus allergen enhances Th1 cytokine responses shown by increased interferon (IFN)-γ/interleukin (IL)-10 ratios as well as enhanced tumor necrosis factor-α release. In response to allergen, zinc increases Treg cells and upregulates the mRNA expression of cytotoxic T-lymphocyte antigen-4 in atopic subjects. Interestingly, Zn50 alone leads to an increase of CD4+CD25high(hi)+ cells in atopic and non-atopic subjects.

Conclusions

Zinc may regulate unwanted hyperresponsive immune reactions by suppressing proliferation through a significant shift from IL-10 to the Th1 cytokine IFN-γ, and enhanced regulatory T cell numbers. Therefore, zinc supplementation may be a promising tool for the therapy of allergies, without negatively affecting the immune system.

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Acknowledgments

We acknowledge grant support SFB/TR22 A03 and Z01 from the Deutsche Forschungsgemeinschaft for A.P. L.R. is a member of the European COST action Zinc-Net (TDI304).

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Authors and Affiliations

  1. Institute of Immunology, Faculty of Medicine, University Hospital, RWTH Aachen University, Pauwelstr. 30, 52074, Aachen, Germany

    Eva Rosenkranz, Peter Uciechowski, Birgit Plümäkers & Lothar Rink

  2. Institute of Medical Statistics, Faculty of Medicine, RWTH Aachen University, Aachen, Germany

    Ralf-Dieter Hilgers

  3. Division of Clinical and Molecular Allergology, Research Center Borstel, Airway Research Center North (ARCN), Borstel, Germany

    Arnd Petersen

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  1. Eva Rosenkranz
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  2. Ralf-Dieter Hilgers
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  3. Peter Uciechowski
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  4. Arnd Petersen
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  5. Birgit Plümäkers
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  6. Lothar Rink
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Corresponding author

Correspondence to Lothar Rink.

Ethics declarations

The study was approved by the local ethical committee (No. AZ 016/09) and had therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study.

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The authors declare that they have no conflict of interest.

Additional information

Arnd Petersen is the Member of the German Center for Lung Research (DZL), Borstel, Germany.

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Rosenkranz, E., Hilgers, RD., Uciechowski, P. et al. Zinc enhances the number of regulatory T cells in allergen-stimulated cells from atopic subjects. Eur J Nutr 56, 557–567 (2017). https://doi.org/10.1007/s00394-015-1100-1

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