title: Induction of regulatory T cells in Th1-/Th17-driven experimental autoimmune encephalomyelitis by zinc administration.
abstract: The essential trace element zinc is indispensable for proper immune function as zinc deficiency accompanies immune defects and dysregulations like allergies, autoimmunity and an increased presence of transplant rejection. This point to the importance of the physiological and dietary control of zinc levels for a functioning immune system. This study investigates the capacity of zinc to induce immune tolerance. The beneficial impact of physiological zinc supplementation of 6 μg/day (0.3mg/kg body weight) or 30 μg/day (1.5mg/kg body weight) on murine experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis with a Th1/Th17 (Th, T helper) cell-dominated immunopathogenesis, was analyzed. Zinc administration diminished EAE scores in C57BL/6 mice in vivo (P<.05), reduced Th17 RORγT(+) cells (P<.05) and significantly increased inducible iTreg cells (P<.05). While Th17 cells decreased systemically, iTreg cells accumulated in the central nervous system. Cumulatively, zinc supplementation seems to be capable to induce tolerance in unwanted immune reactions by increasing iTreg cells. This makes zinc a promising future tool for treating autoimmune diseases without suppressing the immune system.
authors.affiliation: Institute of Immunology, Faculty of Medicine, RWTH Aachen University, University Hospital, Pauwelstrasse 30, 52074 Aachen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Rosenkranz
authors.affiliation: Institute of Immunology, Faculty of Medicine, RWTH Aachen University, University Hospital, Pauwelstrasse 30, 52074 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, Pauwelstrasse 30, 52074 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, Pauwelstrasse 30, 52074 Aachen, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Brieger
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, University Hospital, Pauwelstrasse 30, 52074 Aachen, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Clarner
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, University Hospital, Pauwelstrasse 30, 52074 Aachen, Germany; Department of Neuroanatomy, Ludwig-Maximilians University of Munich, Pettenkoferstrasse 11, 80336 Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Kipp
authors.affiliation: Institute of Immunology, Faculty of Medicine, RWTH Aachen University, University Hospital, Pauwelstrasse 30, 52074 Aachen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Plümäkers
authors.affiliation: Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Meyer
authors.affiliation: Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schwerdtle
authors.affiliation: Institute of Immunology, Faculty of Medicine, RWTH Aachen University, University Hospital, Pauwelstrasse 30, 52074 Aachen, Germany. Electronic address: LRink@UKAachen.de.
authors.forename: Lothar
authors.initials: L
authors.lastname: Rink
mesh_terms: D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D015032:Zinc / Q000008:administration & dosage*
chemical_list: D015032:Zinc
keywords: Experimental autoimmune encephalomyelitis (EAE); Foxp3; Mixed lymphocyte culture (MLC); Regulatory T cells (Treg); Th17; Zinc