Influence of zinc deficiency and supplementation on NK cell cytotoxicity

Rolles, Benjamin; Maywald, Martina; Rink, Lothar

doi:10.1016/j.jff.2018.07.027

Cited by 34 publications

(21 citation statements)

References 41 publications

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“…For a physiological inflammatory response and phagocytic activity macrophages need sufficient intracellular zinc levels ( 1 ). In addition, for NK cells and cytotoxic T cells it was shown that zinc supplementation increased their cytotoxicity toward target cells ( 1 , 2 , 95 ) ( Figures 1.7,1.10 ).…”

Section: Zinc Balances the Immune Response During Infectious Diseasesmentioning

confidence: 97%

The Potential Impact of Zinc Supplementation on COVID-19 Pathogenesis

2020

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During the current corona pandemic, new therapeutic options against this viral disease are urgently desired. Due to the rapid spread and immense number of affected individuals worldwide, cost-effective, globally available, and safe options with minimal side effects and simple application are extremely warranted. This review will therefore discuss the potential of zinc as preventive and therapeutic agent alone or in combination with other strategies, as zinc meets all the above described criteria. While a variety of data on the association of the individual zinc status with viral and respiratory tract infections are available, study evidence regarding COVID-19 is so far missing but can be assumed as was indicated by others and is detailed in this perspective, focusing on re-balancing of the immune response by zinc supplementation. Especially, the role of zinc in viral-induced vascular complications has barely been discussed, so far. Interestingly, most of the risk groups described for COVID-19 are at the same time groups that were associated with zinc deficiency. As zinc is essential to preserve natural tissue barriers such as the respiratory epithelium, preventing pathogen entry, for a balanced function of the immune system and the redox system, zinc deficiency can probably be added to the factors predisposing individuals to infection and detrimental progression of COVID-19. Finally, due to its direct antiviral properties, it can be assumed that zinc administration is beneficial for most of the population, especially those with suboptimal zinc status.

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Section: Zinc Balances the Immune Response During Infectious Diseasesmentioning

confidence: 97%

The Potential Impact of Zinc Supplementation on COVID-19 Pathogenesis

2020

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“…Furthermore, NK cell function was weakened when zinc signals are absent. In this regard, recognition of major histocompatibility complex class I (MHC-I) on target cells, as well as lytic activity, was decreased [ 87 , 88 , 89 , 90 ]. In contrast, zinc supplementation increased differentiation of CD341 progenitors toward NK cells and their cytotoxic activity [ 91 ], as well as NK killing activity, and intracellular perforin concentrations [ 90 ].…”

Section: Immune Function During Zinc Deficiencymentioning

confidence: 99%

Zinc as a Gatekeeper of Immune Function

2017

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After the discovery of zinc deficiency in the 1960s, it soon became clear that zinc is essential for the function of the immune system. Zinc ions are involved in regulating intracellular signaling pathways in innate and adaptive immune cells. Zinc homeostasis is largely controlled via the expression and action of zinc “importers” (ZIP 1–14), zinc “exporters” (ZnT 1–10), and zinc-binding proteins. Anti-inflammatory and anti-oxidant properties of zinc have long been documented, however, underlying mechanisms are still not entirely clear. Here, we report molecular mechanisms underlying the development of a pro-inflammatory phenotype during zinc deficiency. Furthermore, we describe links between altered zinc homeostasis and disease development. Consequently, the benefits of zinc supplementation for a malfunctioning immune system become clear. This article will focus on underlying mechanisms responsible for the regulation of cellular signaling by alterations in zinc homeostasis. Effects of fast zinc flux, intermediate “zinc waves”, and late homeostatic zinc signals will be discriminated. Description of zinc homeostasis-related effects on the activation of key signaling molecules, as well as on epigenetic modifications, are included to emphasize the role of zinc as a gatekeeper of immune function.

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“…In general, existing studies for NK cells are limited to experiments, where zinc has been extracellularly added, whereas effects of altered intracellular zinc homeostasis can only be assumed, as measurements of intracellular zinc levels after stimulation are not available. Only some very recent data are available that showed a zinc flux shortly after IL-1 stimulation [ 85 ]. However, NK cells carry a variety of cell surface receptors, essential for fine tuning of their activities, which contain tyrosine phosphorylation sides such as immunoreceptor tyrosine-based activation motif (ITAM) or immunoreceptor tyrosine-based inhibitory motif (ITIM).…”

Section: From Altered Zinc Homeostasis Via Signaling To Innate Immmentioning

confidence: 99%

Zinc Signals and Immunity

Maywald

Weßels

Rink

2017

IJMS

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Zinc homeostasis is crucial for an adequate function of the immune system. Zinc deficiency as well as zinc excess result in severe disturbances in immune cell numbers and activities, which can result in increased susceptibility to infections and development of especially inflammatory diseases. This review focuses on the role of zinc in regulating intracellular signaling pathways in innate as well as adaptive immune cells. Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article. In addition, the interplay of zinc homeostasis and the redox metabolism in affecting intracellular signaling will be emphasized. Key signaling pathways will be described in detail for the different cell types of the immune system. In this, effects of fast zinc flux, taking place within a few seconds to minutes will be distinguish from slower types of zinc signals, also designated as “zinc waves”, and late homeostatic zinc signals regarding prolonged changes in intracellular zinc.

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Influence of zinc deficiency and supplementation on NK cell cytotoxicity

Cited by 34 publications

References 41 publications

The Potential Impact of Zinc Supplementation on COVID-19 Pathogenesis

The Potential Impact of Zinc Supplementation on COVID-19 Pathogenesis

Zinc as a Gatekeeper of Immune Function

Zinc Signals and Immunity

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