Zinc as a Gatekeeper of Immune Function

Nutrients. 2017 Nov 25;9(12):1286. doi: 10.3390/nu9121286.


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.

Keywords: homeostatic zinc signal; immune function; signaling pathways; zinc deficiency; zinc flux; zinc wave.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / pharmacology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Dietary Supplements
  • Epigenesis, Genetic
  • Homeostasis / drug effects
  • Humans
  • Immune System / drug effects*
  • Immunity, Innate / drug effects
  • Killer Cells, Natural / immunology
  • Phosphoric Monoester Hydrolases / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Zinc / deficiency*
  • Zinc / immunology*
  • Zinc / pharmacology


  • Anti-Inflammatory Agents
  • Antioxidants
  • Carrier Proteins
  • Transcription Factors
  • zinc-binding protein
  • Protein-Tyrosine Kinases
  • Phosphoric Monoester Hydrolases
  • Zinc