ArticleScience advances2022
Plasma iron controls neutrophil production and function.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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
54 citing papers in PubMed, 62 citations in OpenAlex.
- Adjudication of Hospitalizations and Deaths in the IRONMAN Trial of Intravenous Iron for Heart Failure.Journal of the American College of Cardiology · 2024Trial
- The Gut-Iron-Immune Axis in Severe Anaemia and Bacteraemia.Nutrients · 2026Review
- Review
- From Iron to Depression: The Crosstalk Between the Periphery and Brain.Neuroscience bulletin · 2026Review
- Iron and the lung: emerging roles of iron metabolism in pulmonary disease pathogenesis and therapy.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Evaluation of neutrophil oxidative burst capacity in relation to major adverse cardiac events and infection in patients with cardiovascular disease.Clinical research in cardiology : official journal of the German Cardiac Society · 2026Article
- A 'Tangled Web' in the CNS: unraveling neutrophil extracellular traps in neurological disorders.Molecular neurodegeneration · 2026Review
- Plasmacytoid Dendritic Cells Exhibit High Transferrin Receptor Expression Without Iron Accumulation.European journal of immunology · 2026Article
- Prognostic role of anaemia in maxillofacial space infections: a prospective clinical cohort study.Oral and maxillofacial surgery · 2026Article
- Genetic regulation of AIF1 shapes immune and liver injury profiles in chronic alcohol use.JCI insight · 2026Article
- Naringenin ameliorates swine pulpitis by modulating immune response.BMC oral health · 2026Article
- Reduced gastrointestinal iron uptake in pulmonary arterial hypertension: a prospective cross-sectional study.Respiratory research · 2026Article
- Iron deficiency aggravates hepatic inflammation in suckling piglets via endoplasmic reticulum stress-driven NF-κB pathway activation.Journal of animal science and biotechnology · 2026Article
- Iron status modulates immune cell proportions to drive epigenetic age acceleration: A 2-step Mendelian randomization study.Medicine · 2026Article
- Iron and metabolic rewiring in cancer.Oncogenesis · 2026Review
- Functional alterations of neutrophils from β-thalassemia patients exposed to Pythium insidiosum: An ex vivo study.PloS one · 2026Article
- Effects of essential metals (iron, zinc, and copper) on thyroid diseases - a narrative review.Frontiers in medicine · 2026Review
- Iron as an immunometabolic signal in infection and inflammation.Frontiers in immunology · 2026Review
- Neutrophil extracellular traps contribute significantly to vascular dysfunction in sepsis.Frontiers in pharmacology · 2026Review
- Iron and the immune system.Nature reviews. Immunology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Low plasma iron (hypoferremia) induced by hepcidin is a conserved inflammatory response that protects against infections but inhibits erythropoiesis. How hypoferremia influences leukocytogenesis is unclear. Using proteomic data, we predicted that neutrophil production would be profoundly more iron-demanding than generation of other white blood cell types. Accordingly in mice, hepcidin-mediated hypoferremia substantially reduced numbers of granulocytes but not monocytes, lymphocytes, or dendritic cells. Neutrophil rebound after anti-Gr-1-induced neutropenia was blunted during hypoferremia but was rescued by supplemental iron. Similarly, hypoferremia markedly inhibited pharmacologically stimulated granulopoiesis mediated by granulocyte colony-stimulating factor and inflammation-induced accumulation of neutrophils in the spleen and peritoneal cavity. Furthermore, hypoferremia specifically altered neutrophil effector functions, suppressing antibacterial mechanisms but enhancing mitochondrial reactive oxygen species-dependent NETosis associated with chronic inflammation. Notably, antagonizing endogenous hepcidin during acute inflammation enhanced production of neutrophils. We propose plasma iron modulates the profile of innate immunity by controlling monocyte-to-neutrophil ratio and neutrophil activity in a therapeutically targetable system.
Identifiers
What OpenQuestion holds
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.