title: Zinc supplementation augments TGF-β1-dependent regulatory T cell induction.
abstract: Regulatory T cells (Treg) play a pivotal role in immune regulation. For proper immune function, also trace elements such as zinc, and anti-inflammatory cytokines, including transforming growth factor beta 1 (TGF-β1) and interleukin (IL)-10 are indispensable. Hence, in this study the influence of TGF-β1, IL-10, and zinc supplementation on Treg cells differentiation was investigated.
  
  
  
  A synergistic effect of a combined zinc and TGF-β1 treatment on Foxp3 expression in peripheral blood mononuclear cells and mixed lymphocyte cultures (MLC) was found by performing Western blot analysis. Additionally, combined treatment causes elevated Smad 2/3 phosphorylation, which plays an important role in Foxp3 expression. This is due to a TGF-β1-mediated increase of intracellular-free zinc measured by zinc probes Fluozin3-AM and ZinPyr-1. Moreover, zinc as well as TGF-β1 treatment caused significantly reduced interferon (IFN)-γ secretion in MLC.
  
  
  
  Combined zinc and TGF-β1 treatment provoked an increased Treg cell induction due to a triggered intracellular zinc signal, which in association with an increased Smad 2/3 activation leads to a boosted Foxp3 expression and resulting in an ameliorated allogeneic reaction in MLC. Thus, zinc can be used as a favorable additive to elevate the induction of Treg cells in adverse immune reactions.
authors: Institute of Immunology, Faculty of Medicine, RWTH Aachen University Hospital, Aachen, Germany.
authors: Martina
authors: M
authors: Maywald
authors: Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, Faculty of Medicine, RWTH Aachen University Hospital, Aachen, Germany.
authors: Steffen K
authors: SK
authors: Meurer
authors: Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, Faculty of Medicine, RWTH Aachen University Hospital, Aachen, Germany.
authors: Ralf
authors: R
authors: Weiskirchen
authors: Institute of Immunology, Faculty of Medicine, RWTH Aachen University Hospital, Aachen, Germany.
authors: Lothar
authors: L
authors: Rink
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D019587:Dietary Supplements; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D007371:Interferon-gamma; D015032:Zinc
keywords: Foxp3; Regulatory T cells; Smad signaling; TGF-β1; Zinc