title: Modulatory effects of low-dose hydrogen peroxide on the function of human plasmacytoid dendritic cells.
abstract: Under normal conditions, plasmacytoid dendritic cells (pDCs) are located in peripheral lymphoid organs or circulate in the blood, from where they can migrate to sites of infection or inflammation. In inflamed tissues, pDCs can be exposed to elevated levels of reactive oxygen species produced by inflammatory cells and we presume that oxidative stress could affect the cellular responses of pDCs to microenvironmental stimuli. To explore this possibility, human pDCs isolated from peripheral blood of healthy donors were treated with H(2)O(2) and R837 (a Toll-like receptor 7 ligand), separately and in combination. Our results demonstrate that treatment with a low concentration (0.01 μM) of H(2)O(2) resulted in only slight changes in the expression of CD40, CD80, CD86, and CD83; however, low-dose H(2)O(2) markedly decreased the expression of HLA-DQ on pDCs. Exposure to H(2)O(2) did not trigger the release of IL-6, TNF-α, IL-8, or IFN-α from pDCs. Although addition of H(2)O(2) did not modify the capacity of pDCs to activate allogeneic IL-17- or IFN-γ-producing T cells, it significantly increased the ability of pDCs to stimulate IL-4-secreting T cells. Exposure of pDCs to H(2)O(2) before cocultivation with naïve autologous T cells significantly lowered IL-10 production by T cells, but did not affect IL-17 release. It was also observed that H(2)O(2)-exposed pDCs provided stronger stimuli for Th2 than for Th1 differentiation upon autologous activation, compared to untreated pDCs, possibly because of elevated surface expression of OX40-L. Most importantly, when pDCs were stimulated with R837 in the presence of H(2)O(2), decreased phenotypic activation, decreased chemokine and cytokine release, and impaired allo- and autostimulatory functions of pDCs were detected, indicating that pDCs exposed to oxidative stress in vivo may have an anti-inflammatory or tolerogenic role in regulating adaptive immune responses.
authors.affiliation: Department of Immunology, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen H-4012, Hungary.
authors.forename: Kitti
authors.initials: K
authors.lastname: Pazmandi
authors.affiliation: Department of Immunology, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen H-4012, Hungary.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Magyarics
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors.forename: Istvan
authors.initials: I
authors.lastname: Boldogh
authors.affiliation: Department of Immunology, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen H-4012, Hungary.
authors.forename: Aniko
authors.initials: A
authors.lastname: Csillag
authors.affiliation: Department of Immunology, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen H-4012, Hungary.
authors.forename: Eva
authors.initials: E
authors.lastname: Rajnavolgyi
authors.affiliation: Department of Immunology, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen H-4012, Hungary. Electronic address: bacsi.attila@gmail.com.
authors.forename: Attila
authors.initials: A
authors.lastname: Bacsi
mesh_terms: D056704:Adaptive Immunity; D015703:Antigens, CD / Q000378:metabolism; D016764:Cell Polarity; D002470:Cell Survival; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress; D010641:Phenotype; D011804:Quinolines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000378:metabolism
chemical_list: C557465:1-(2-methylpropyl)-1H-imidazo(4,5-c)quinolin 4-amine; D015703:Antigens, CD; D018925:Chemokines; D016877:Oxidants; D011804:Quinolines; D017382:Reactive Oxygen Species; D051199:Toll-Like Receptor 7; D006861:Hydrogen Peroxide