Work

Selective impact of zinc on human circulating CD56dim NK cells

Year: 2025

Type: article

Abstract: Natural Killer (NK) cells are essential for recognizing aberrant and virus-infected cells. Adequate levels of the trace element zinc are known to be important for proper immune functionality against infections and tumor growth. So far, not many studies have analyzed the effects of zinc on NK cells. We previously observed higher levels of activated CD69 + NK cells in zinc-adequate compared to zinc-deficient donors. We therefore aimed to analyze the influence of zinc on the activation and functionality of NK cell in vitro . Peripheral blood mononuclear cells were freshly isolated from young healthy donors. Serum zinc levels and Adjusted Zinc Diet Score (AZDS) were determined. NK cells, CD56 dim NK cells, and CD56 bright NK cells were analyzed ex vivo or cultivated in zinc-deficient, zinc-adequate, and zinc-supplemented media for 1 or 20 h ± specific inhibitors. CD56 dim NK cell frequencies, phenotype, and functionality were analyzed via flow cytometry, qPCR, and Western blot. The frequencies of cytotoxic CD56 dim NK cells positively correlated with serum zinc as well as AZDS. CD69 expression was significantly increased after 20 h of zinc supplementation on CD56 dim NK cells. CD69 + CD56 dim NK cells showed significant higher degranulation capacity and IFNγ production. Furthermore, NFκB inhibition upregulated CD69 expression and NFKB mRNA was significantly decreased in zinc-supplemented conditions. In addition, perforin levels were sensitive to zinc deprivation. Extracellular zinc selectively activates CD56 dim NK cells enhancing degranulation and IFNγ production. Zinc supplementation might be a useful tool for in vitro NK cell expansion protocols for future cellular therapies. • Frequencies of CD56 dim NK cells positively correlate with serum zinc and Adjusted Zinc Diet Score • CD56 dim NK cells upregulate CD69 expression after 20 h of in vitro zinc supplementation • CD69 + CD56 dim NK cells show significantly higher degranulation capacity and IFNγ production • Perforin is sensitive to zinc deprivation

Source: Journal of Trace Elements in Medicine and Biology

DOI: 10.1016/j.jtemb.2025.127788

Authors: Sabrina B. Bennstein, Ronja Stöcker, Laura Heenen, Jana Jakobs, Kim Ohl, Lothar Rink

Institution: RWTH Aachen University

Language: English

Topic: Immune Cell Function and Interaction

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,700