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 epsilon RI)-induced cytokine production was diminished, but degranulation was intact. Znt5 was involved in Fc epsilon RI-induced translocation of protein kinase C (PKC) to the plasma membrane and the nuclear translocation of nuclear factor kappa 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.