Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function.
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.
Kitamura
Hidemitsu
H
Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Kanagawa 230-0045, Japan.
Morikawa
Hideyuki
H
Kamon
Hokuto
H
Iguchi
Megumi
M
Hojyo
Shintaro
S
Fukada
Toshiyuki
T
Yamashita
Susumu
S
Kaisho
Tsuneyasu
T
Akira
Shizuo
S
Murakami
Masaaki
M
Hirano
Toshio
T
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
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