The Interaction of Sodium and Zinc in the Priming of T Cell Subpopulations Regarding Th17 and Treg Cells

Mol Nutr Food Res. 2020 Jan;64(2):e1900245. doi: 10.1002/mnfr.201900245. Epub 2020 Jan 7.

Abstract

Scope: Nutrition is a critical determinant of a functional immune system. The aim of this study is to investigate the molecular mechanisms by which immune cells are influenced by zinc and sodium.

Methods and results: Mixed lymphocyte cultures and Jurkat cells are generated and incubated with zinc, sodium, or a combination of both for further tests. Zinc induces the number of regulatory T cells (Treg) and decreases T helper 17 cells (Th17), and sodium has the opposite effect. The transforming growth factor beta receptor signaling pathway is also enhanced by zinc and reduced by sodium as indicated by contrary phosphoSmad 2/3 induction. Antagonistic effects can also be seen on zinc transporter and metallothionein-1 (MT-1) mRNA expression: zinc declines Zip10 mRNA expression while sodium induces it, whereas MT-1 mRNA expression is induced by zinc while it is reduced by sodium.

Conclusion: This data indicate that zinc and sodium display opposite effects regarding Treg and Th17 induction in MLC, respectively, resulting in a contrary effect on the immune system. Additionally, it reveals a direct interaction of zinc and sodium in the priming of T cell subpopulations and shows that Zip10 and MT-1 play a significant role in those differentiation pathways.

Keywords: Foxp3; T helper 17 cells; regulatory T cells; sodium; zinc.

MeSH terms

  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism
  • Cells, Cultured
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Jurkat Cells
  • Metallothionein / genetics
  • Metallothionein / metabolism
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Phosphoric Monoester Hydrolases / metabolism
  • Signal Transduction / drug effects
  • Smad Proteins / metabolism
  • Sodium / metabolism
  • Sodium / pharmacology*
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / physiology
  • Th17 Cells / drug effects*
  • Th17 Cells / physiology
  • Zinc / metabolism
  • Zinc / pharmacology*

Substances

  • Cation Transport Proteins
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RORC protein, human
  • SLC39A10 protein, human
  • Smad Proteins
  • Metallothionein
  • Sodium
  • Phosphoric Monoester Hydrolases
  • Zinc