Table 1.

Effect of zinc signals on Immune function: Altered immunological functions can be induced by different zinc signals, as zinc flux, zinc wave, and homeostatic zinc signal. Altered from [59].

Zinc Signal	Duration	Effect
Zinc Flux	Seconds/minutes	▪Inhibition of PDE in monocytes/macrophages [60] ▪Inhibition of MKP in monocytes/macrophages [61,62] ▪Induction of PMA-triggered NET-formation in PMN [40] ▪Induction of Lck recruitment to TCR [63,64] ▪Zinc release from lysosomes in T cells [65] ▪Triggering T cell activation by APC [66] ▪Induction of Lck homodimerization/activation in T cells [67] ▪Redistribution of zinc from nucleus/mitochondria to cytosol/microsomes [30]
Zinc wave	Minutes	▪Zinc release from perinuclear area in mast cells [57]
homeostatic Zinc Signal	Hours	▪Stabilization of MyD88 expression [5,68] ▪Induction of A20 expression in T cells, monocytes [69] ▪Negative regulation of IRAK signaling [70,71] ▪MAPK activation in immune cells [72,73,74] ▪Negative regulation of TRIF pathway in macrophages [5] ▪Changed Zip and ZnT expression in DCs and T cells [58,72] ▪Inhibition of AC transcription in T cells [75] ▪Influence of cytokine production, e.g., IL-2 in T cells [72] ▪Induction of Akt/ERK/p38 phosphorylation in T cells [73] ▪Triggering of PTEN degradation in T cells [76] ▪Inhibition of IL-6/IL-1 induced STAT3 phosphorylation [77] ▪Alteration of M1/M2 differentiation by inhibition of STAT6 phosphorylation [78] ▪Induction/stabilization of regulatory T cells [79,80] ▪Inhibition of Th17 and Th9 cell differentiation [81,82] ▪Reduced cytokine production, e.g., IFN-γ in T cells [83] ▪Induction of NK cell killing and granzyme expression [84,85] ▪Inhibition of caspase activity ▪Inhibition of cAMP/cGMP hydrolysis [86,87] ▪Inhibition of DNA fragmentation [6] ▪Epigenetic modifications due to inhibition of SIRT1 [79] ▪Inhibition of IL-1/TNF CRP expression in myeloid cells [53,69,88]

AC: adenylate cyclase; cAMP: cyclic adenosine monophosphate; cGMP: cyclic guanine monophosphate; CRP: c-reactive protein; DC: dendritic cell; IL: interleukin; IFN: interferon; IRAK: interleukin-1 receptor-associated kinase; Lck: lymphocyte-specific protein tyrosine kinas; MAPK: mitogen-activated protein kinase; MKP: MAP-kinase phosphatase; MyD88: myeloid differentiation primary response gene 88; NET: neutrophil extracellular traps; NK: natural killer; PDE: phosphodiesterase; PMA: Phorbol-12-myristat-13-acetat; PTEN: phosphatase and tensin homolog deleted on chromosome 10; STAT: signal transducers and activators of transcription; TCR: T cell receptor; APC: Antigen presenting cell; Th: T helper; TNF: tumor necrosis factor; TRIF: Toll-interleukin-1 receptor (TIR) domain-containing adaptor-inducing interferon.