ArticleJournal of leukocyte biology2009
Zinc transporter ZIP8 (SLC39A8) and zinc influence IFN-gamma expression in activated human T cells.
Article in Journal of leukocyte biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
138 citing papers in PubMed, 1 synthesis or guideline pooled it, 226 citations in OpenAlex.
- Pooled it
- Trial
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- The Dual Role of Zinc Homeostasis in Gram-Negative Bacterial Pathogenicity and Host Immune Defense.Microorganisms · 2026Review
- Review
- Article
- Manganese: biology, physiology and role in disease.Cell discovery · 2026Review
- Junctions, Transporters, and Interactions of Endothelial Cells: Regulation by Ethanol.International journal of molecular sciences · 2026Review
- ZIP3 is essential for the encephalitogenic function of pTh17 cells by regulating intracellular zinc levels.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2026Article
- Zinc Supplementation Partially Reconstitutes Impaired Interferon-γ Production in the Elderly.International journal of molecular sciences · 2026Article
- Immunometabolic control of cytokine production by micronutrients in health, aging, and inflammation.Frontiers in immunology · 2026Review
- A homology-based 3D model and structure-function studies reveal key elements for divalent metal ion transporter ZIP8 (SLC39A8) function.The Journal of biological chemistry · 2025Article
- Removal of Toxic Metabolites-Chelation: Manganese Disorders.Journal of inherited metabolic disease · 2025Review
- Article
- Zrt-Irt-like Proteins (ZIP) Family Zinc Transporters: Emerging Players in Pancreatic β Cell Function and Insulin Regulation.The Journal of nutrition · 2025Review
- Increase of Intracellular Zinc Levels Rather Than Zinc Influx Inhibits Interleukin-2 Production in Zinc Supplemented Jurkat Cells.Cell biochemistry and function · 2025Article
- Zinc-mediated dynamics of CD4/CD8α co-receptors and Lck kinase: implications for zinc homeostasis, immune response, and biotechnological innovations.Metallomics : integrated biometal science · 2025Review
- Zinc deficiency as possible link between immunosenescence and age-related diseases.Immunity & ageing : I & A · 2025Review
- Metal-modulated T cell antitumor immunity and emerging metalloimmunotherapy.Cancer metastasis reviews · 2025Review
- Human genetic variants in SLC39A8 impact uptake and steady-state metal levels within the cell.Life science alliance · 2025Article
78 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The zinc transporter ZIP8 is highly expressed in T cells derived from human subjects. T cell ZIP8 expression was markedly up-regulated upon in vitro activation. T cells collected from human subjects who had received oral zinc supplementation (15 mg/day) had higher expression of the activation marker IFN-gamma upon in vitro activation, indicating a potentiating effect of zinc on T cell activation. Similarly, in vitro zinc treatment of T cells along with activation resulted in increased IFN-gamma expression with a maximum effect at 3.1 microM. Knockdown of ZIP8 in T cells by siRNA decreased ZIP8 levels in nonactivated and activated cells and concomitantly reduced secretion of IFN-gamma and perforin, both signatures of activation. Overexpression of ZIP8 by transient transfection caused T cells to exhibit enhanced activation. Confocal microscopy established that ZIP8 is localized to the lysosome where ZIP8 abundance is increased upon activation. Loss of lysosomal labile zinc in response to activation was measured by flow cytometry using a zinc fluorophore. Zinc between 0.8 and 3.1 microM reduced CN phosphatase activity. CN was also inhibited by the CN inhibitor FK506 and ZIP8 overexpression. The results suggest that zinc at low concentrations, through inhibition of CN, sustains phosphorylation of the transcription factor CREB, yielding greater IFN-gamma expression in T cells. ZIP8, through control of zinc transport from the lysosome, may provide a secondary level of IFN-gamma regulation in T cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.