Roles of Zinc Signaling in the Immune System

Figure 5

Zn uptake via ZIP6 and ZIP8 potentiates TCR signaling. Through the interaction of DCs and T cells, TCR activation rapidly increases cytoplasmic Zn concentrations, particularly at the subsynaptic compartment, in a manner dependent on ZIP6 (blue). The enhanced influx of Zn reduces SHP-1 recruitment to the TCR activation complex, thereby augmenting ZAP70 activation and leading to a sustained influx of calcium. On the other hand, TCR activation increases ZIP8 expression, which exports Zn out of the lysosome and into the cytoplasm (red). The resultant increase in cytoplasmic Zn inhibits CN, leading to increased CREB activation and the subsequent expression of IFN-γ. Thus, Zn facilitates TCR’s functions in proliferation and IFN-γ production.