title: Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function.
abstract: Zinc is a trace element that is essential for the function of many enzymes and transcription factors. Zinc deficiency results in defects in innate and acquired immune responses. However, little is known about the mechanism(s) by which zinc affects immune cell function. Here we show that stimulation with the Toll-like receptor 4 agonist lipopolysaccharide (LPS) altered the expression of zinc transporters in dendritic cells and thereby decreased intracellular free zinc. A zinc chelator mimicked the effects of LPS, whereas zinc supplementation or overexpression of the gene encoding Zip6, a zinc transporter whose expression was reduced by LPS, inhibited LPS-induced upregulation of major histocompatibility complex class II and costimulatory molecules. These results establish a link between Toll-like receptor signaling and zinc homeostasis.
authors.affiliation: Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Kanagawa 230-0045, Japan.
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Kitamura
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Morikawa
authors.forename: Hokuto
authors.initials: H
authors.lastname: Kamon
authors.forename: Megumi
authors.initials: M
authors.lastname: Iguchi
authors.forename: Shintaro
authors.initials: S
authors.lastname: Hojyo
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukada
authors.forename: Susumu
authors.initials: S
authors.lastname: Yamashita
authors.forename: Tsuneyasu
authors.initials: T
authors.lastname: Kaisho
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Masaaki
authors.initials: M
authors.lastname: Murakami
authors.forename: Toshio
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics*; D002454:Cell Differentiation; D002614:Chelating Agents / Q000494:pharmacology; D003713:Dendritic Cells / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D015870:Gene Expression / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000378:metabolism; D006706:Homeostasis; D008070:Lipopolysaccharides / Q000494:pharmacology; D052119:Lysosomal-Associated Membrane Protein 2 / Q000032:analysis / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation; D015032:Zinc / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D027682:Cation Transport Proteins; D002614:Chelating Agents; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D052119:Lysosomal-Associated Membrane Protein 2; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D015032:Zinc