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¹ Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan
² Immune system, Cooperation Program, Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan
³ Laboratory of Developmental Immunology and the Core Research for Evolutional Science and Technology Program (CREST) of the Japan Science and Technology Agency, Graduate School of Frontier Biosciences, Graduate School of Medicine, and WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0817, Japan
⁴ Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan
⁵ Atopy Research Center, Juntendo University, Tokyo 113-8421, Japan
⁶ Frontier Research Initiative, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

CORRESPONDENCE Toshio Hirano: hirano{at}molonc.med.osaka-u.ac.jp

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 receptor I (FcRI)–induced cytokine production was diminished, but degranulation was intact. Znt5 was involved in FcRI-induced translocation of protein kinase C (PKC) to the plasma membrane and the nuclear translocation of nuclear factor B. 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.

Abbreviations used: BMMC, BM-derived mast cell; cDNA, complementary DNA; CHS, contact hypersensitivity; DAG, diacylglycerol; ERK, extracellular signal-regulated kinase; FcRI, Fc receptor I; MAPK, mitogen-activated protein kinase; mRNA, messenger RNA; PCA, passive cutaneous anaphylaxis; PKC, protein kinase C; PVDF, polyvinylidine fluoride; Slc, solute-linked carrier; Zip, ZRT/IRT-related protein; Zn, zinc; Znt, Zn transporter.

© 2009 Nishida et al.
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