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

Abstract 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, focussing on the TH 1-dominated allogeneic immune reaction. Allogeneic immune reaction was modelled 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 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. 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 celltype while not suppressing the immune system. This article is protected by copyright. All rights reserved.