title: Zinc supplementation induces regulatory T cells by inhibition of Sirt-1 deacetylase in mixed lymphocyte cultures.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Institute of Immunology, Faculty of Medicine, RWTH Aachen University, University Hospital, Aachen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Rosenkranz
authors.affiliation: Institute of Immunology, Faculty of Medicine, RWTH Aachen University, University Hospital, Aachen, Germany.
authors.forename: Claudia H D
authors.initials: CH
authors.lastname: Metz
authors.affiliation: Institute of Immunology, Faculty of Medicine, RWTH Aachen University, University Hospital, Aachen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Maywald
authors.affiliation: Institute of Medical Statistics, Faculty of Medicine, RWTH Aachen University, University Hospital, Aachen, Germany.
authors.forename: Ralf-Dieter
authors.initials: RD
authors.lastname: Hilgers
authors.affiliation: Institute of Immunology, Faculty of Medicine, RWTH Aachen University, University Hospital, Aachen, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Weßels
authors.affiliation: Institute of Immunology, Faculty of Medicine, RWTH Aachen University, University Hospital, Aachen, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Senff
authors.affiliation: Institute of Immunology, Faculty of Medicine, RWTH Aachen University, University Hospital, Aachen, Germany.|Department of Food Chemistry and Toxicology, Berlin Institute of Technology, Berlin, Germany.
authors.forename: Hajo
authors.initials: H
authors.lastname: Haase
authors.affiliation: Institute of Immunology, Faculty of Medicine, RWTH Aachen University, University Hospital, Aachen, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Jäger
authors.affiliation: Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Ott
authors.affiliation: Translational Medicine Group, Cranfield University, Cranfield, Bedfordshire, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Aspinall
authors.affiliation: Institute of Immunology, Faculty of Medicine, RWTH Aachen University, University Hospital, Aachen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Plümäkers
authors.affiliation: Institute of Immunology, Faculty of Medicine, RWTH Aachen University, University Hospital, Aachen, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Rink
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006086:Graft vs Host Disease / Q000517:prevention & control; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology*
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D056572:Histone Deacetylase Inhibitors; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D015032:Zinc
keywords: Foxp3; Regulatory T cells; Sirt-1; Tolerance; Zinc