Zinc signals in immunology

Zinc is known to be an essential trace element that is highly important for all proliferating cells in the human body, especially for the immune system. Free zinc influences several signaling pathways, such as Toll-like receptor 4 or T cell receptor signaling, by binding reversibly to regulatory sites in signaling proteins, resulting in a change of free zinc concentrations that can affect signal transduction, and thus cellular responses can be altered. Zinc signals have been observed in cells of the innate as well as of the adaptive immune system, i.e., neutrophil granulocytes, mast cells, monocytes, dendritic cells, and T cells, mostly in changes of the cytoplasmic zinc concentration. To characterize zinc signals, one can distinguish them by the timescale they take place. First, zinc signals can occur within a few seconds to minutes and are, therefore, called fast zinc signals. Second, a slightly slower type of zinc signal is known and described as “zinc wave.” Third, some zinc signals occur on a timescale significantly longer than the others. In these cases, the signals are typically involved in altered expression of proteins involved in zinc homeostasis. Zinc signals occurring in different cell types and signaling pathways that are mentioned in this chapter are classified regarding the specific discrimination of fast zinc signal, zinc wave, and late zinc signal.