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

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 T_H1-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.