Zinc transporter Znt5/Slc30a5 is required for the mast cell-mediated delayed-type allergic reaction but not the immediate-type reaction.
Zinc (Zn) is an essential nutrient and its deficiency causes immunodeficiency. However, it remains unknown how Zn homeostasis is regulated in mast cells and if Zn transporters are involved in allergic reactions. We show that Znt5/Slc30a5 is required for contact hypersensitivity and mast cell-mediated delayed-type allergic response but not for immediate passive cutaneous anaphylaxis. In mast cells from Znt5(-/-) mice, Fc epsilon receptor I (Fc epsilonRI)-induced cytokine production was diminished, but degranulation was intact. Znt5 was involved in Fc epsilonRI-induced translocation of protein kinase C (PKC) to the plasma membrane and the nuclear translocation of nuclear factor kappaB. In addition, the Zn finger-like motif of PKC was required for its plasma membrane translocation and binding to diacylglycerol. Thus, Znt5 is selectively required for the mast cell-mediated delayed-type allergic response, and it is a novel player in mast cell activation.
Nishida
Keigo
K
Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
Hasegawa
Aiko
A
Nakae
Susumu
S
Oboki
Keisuke
K
Saito
Hirohisa
H
Yamasaki
Satoru
S
Hirano
Toshio
T
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D027682:Cation Transport Proteins; D015550:Cell Degranulation / Q000276:immunology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000276:immunology; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; D015032:Zinc / Q000276:immunology*
D027682:Cation Transport Proteins; D016207:Cytokines; C521907:Fc-epsilon receptor I beta-chain, mouse; D007527:Isoenzymes; D026901:Membrane Transport Proteins; D016328:NF-kappa B; D017455:Receptors, IgE; D011993:Recombinant Fusion Proteins; C486753:Slc30a5 protein, mouse; D011493:Protein Kinase C; D015032:Zinc