Zinc supplementation induces regulatory T cells by inhibition of Sirt-1 deacetylase in mixed lymphocyte cultures

Eva Rosenkranz, Claudia H.D. Metz, Martina Maywald, Ralf Dieter Hilgers, Inga Weßels, Tina Senff, Hajo Haase, Maximilian Jager, Melanie Ott, Richard Aspinall, Birgit Plumakers, Lothar Rink

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31 Citations (Scopus)

Abstract

Scope: Zinc is an essential trace element, regulating immune function. Its deficiency results in immune dysfunction and transplant rejection. In here, a benefit of zinc supplementation for the induction of tolerance was investigated, focusing on the TH1-dominated allogeneic immune reaction. Methods and results: Allogeneic immune reaction was modeled by mixed lymphocyte culture (MLC). The effect of zinc supplementation was monitored via expression of cytokines and surface lineage markers using ELISA and flow cytometry. Epigenetic analyses were performed to investigate mechanisms underlying zinc-induced changes in regulatory T cell (Treg) activation. Results reveal that Tregs are induced when MLCs are treated with 50 μM zinc causing a decrease in IFNγ production. IL-2 and IL-10 expression were not affected. The teleology of this effect includes the inhibition of histone deacetylase Sirt-1-mediated Foxp3 deacetylation, resulting in its decreased degradation. Conclusion: In conclusion, zinc should be considered to prevent graft-versus-host disease (GVHD) as it is capable of stabilizing iTregs, resulting in increased numbers of this cell type while not suppressing the immune system. Zinc is an essential trace element important for immune function. Regulatory T cells (Treg) are key players in the regulation of the immune system, especially in preventing allergic and autoimmune reactions, and transplant rejection. Here, we show, that zinc inhibit Sirt-1, a histondeacetylase, resulting in stabilization of Foxp3, the specific transcription factor of regulatory T cells. The induced (i)Treg reduced allogeneic reaction by downregulation of IFN-γ and upregulation of CD25 and CTLA-4.

Original languageEnglish
Pages (from-to)661-671
Number of pages11
JournalMolecular Nutrition and Food Research
Volume60
Issue number3
Early online date28 Nov 2015
DOIs
Publication statusPublished - 1 Mar 2016
Externally publishedYes

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Keywords

  • Foxp3
  • Regulatory T cells
  • Sirt-1
  • Tolerance
  • Zinc

ASJC Scopus subject areas

  • Biotechnology
  • Food Science

Cite this

Rosenkranz, E., Metz, C. H. D., Maywald, M., Hilgers, R. D., Weßels, I., Senff, T., ... Rink, L. (2016). Zinc supplementation induces regulatory T cells by inhibition of Sirt-1 deacetylase in mixed lymphocyte cultures. Molecular Nutrition and Food Research, 60(3), 661-671. https://doi.org/10.1002/mnfr.201500524