Eva Rosenkranz1, Claudia H D Metz1, Martina Maywald1, Ralf-Dieter Hilgers2, Inga Weßels1, Tina Senff1, Hajo Haase1,3, Maximilian Jäger1, Melanie Ott4, Richard Aspinall5, Birgit Plümäkers1, Lothar Rink1. 1. Institute of Immunology, Faculty of Medicine, RWTH Aachen University, University Hospital, Aachen, Germany. 2. Institute of Medical Statistics, Faculty of Medicine, RWTH Aachen University, University Hospital, Aachen, Germany. 3. Department of Food Chemistry and Toxicology, Berlin Institute of Technology, Berlin, Germany. 4. Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA, USA. 5. Translational Medicine Group, Cranfield University, Cranfield, Bedfordshire, UK.
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 TH 1-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.
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 TH 1-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.
Authors: Mariam Mathew George; Kavitha Subramanian Vignesh; Julio A Landero Figueroa; Joseph A Caruso; George S Deepe Journal: J Immunol Date: 2016-07-27 Impact factor: 5.422