Achievements

Zinc transporter, Znt5/Slc30a5 is required for allergic contact dermatitis .

Zinc is essential nutrient for our body. Therefore, cells have evolved a complex system to maintain a balance of zinc uptake, intracellular storage, and efflux. 22 members of zinc transporter have been reported in mammals. Two solute-linked carrier (Slc) protein families have been identified in zinc transport: the zinc transporter (Znt)/Slc30 and ZRT/IRT-related protein (Zip)/Slc39. Znt transporters reduce cytoplasmic zinc availability by promoting zinc efflux from the cytoplasm into the extracellular space or intracellular compartments. The Zip transporters increase cytoplasmic zinc availability by promoting extracellular zinc uptake and zinc release from compartments into the cytoplasm.
As you know, zinc deficiency causes immunodeficiency. However, it remains unknown how zinc homeostasis is regulated in mast cells and if any zinc transporters are involved in immune response. We found that Znt5/Slc30a5 is required for contact hypersensitivity, mast cell-mediated delayed-type allergic response and cytokine production such as IL-6 and TNF alpha in vivo. Consistent with this, Fc epsilon RI-induced cytokine production was diminished in mast cells from Znt5 KO mice. Furthermore, we showed that Znt5 was involved in Fc epsilon RI-induced translocation of PKC to the plasma membrane.

Thus, controlling intracellular zinc by modulating its transporters might one day provide a way to treat mast cell-mediated allergies and diseases including allergic contact dermatitis.

Zinc transporter Znt5/Slc30a5 is required for the mast cell-mediated delayed-type allergic reaction but not the immediate-type reaction.

Nishida K*., A. Hasegawa*, S. Nakae, K. Oboki, H. Saito, S. Yamasaki, and T. Hirano. (* equal contribution)
J. Exp. Med. 206:1351-1364 (2009) (PubMed) (JEM in this issue)

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Achievements

Zinc transporter, Znt5/Slc30a5 is required for allergic contact dermatitis .