ArticleBlood2015
A novel inflammatory pathway mediating rapid hepcidin-independent hypoferremia.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
What it found
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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.
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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.
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Who cites it
104 citing papers in PubMed, 168 citations in OpenAlex.
- Maternal iron kinetics and maternal-fetal iron transfer in normal-weight and overweight pregnancy.The American journal of clinical nutrition · 2022Trial
- The Effect ofNutrients · 2020Trial
- The effect of BCG on iron metabolism in the early neonatal period: A controlled trial in Gambian neonates.Vaccine · 2015Trial
- Tissue-resident colon macrophages shape the microbiome and regulate mucosal healing via ferroportin.Cell reports · 2026Article
- Article
- Impaired iron balance and erythrocytosis: a complex relationship.Blood cancer journal · 2026Review
- Review
- Iron as an immunometabolic signal in infection and inflammation.Frontiers in immunology · 2026Review
- Hypoferremic Response to Chronic Inflammation Is Controlled via the Hemojuvelin/Hepcidin/Ferroportin Axis and Does Not Involve Hepcidin-Independent Regulation of Fpn mRNA.American journal of hematology · 2025Article
- Improvement of iron status with elexacaftor tezacaftor ivacaftor therapy is associated with the correction of systemic inflammation and improvement of lung function: a one-year prospective study.Scientific reports · 2025Article
- Interplay between iron metabolism, inflammation, and EPO-ERFE-hepcidin axis in RDEB-associated chronic anemia.Blood advances · 2025Article
- Hepatocyte Toll-like receptors contribute to the hepcidin inflammatory response to pathogens and pathogen-derived ligands.HemaSphere · 2025Article
- HFE-Related Hemochromatosis May Be a Primary Kupffer Cell Disease.Biomedicines · 2025Review
- Iron, Hepcidin, and Immunity.Advances in experimental medicine and biology · 2025Review
- Exploring the Causal Relationship Between Inflammatory Cytokines and MRI-Derived Brain Iron: A Mendelian Randomization Study.Brain and behavior · 2024Article
- Redox-Regulated Iron Metabolism and Ferroptosis in Ovarian Cancer: Molecular Insights and Therapeutic Opportunities.Antioxidants (Basel, Switzerland) · 2024Review
- Article
- Mechanisms controlling cellular and systemic iron homeostasis.Nature reviews. Molecular cell biology · 2024Review
- Ferroptosisand Its Role in the Treatment of Sepsis-Related Organ Injury: Mechanisms and Potential Therapeutic Approaches.Infection and drug resistance · 2024Review
- HMGB1 induces hepcidin upregulation in astrocytes and causes an acute iron surge and subsequent ferroptosis in the postischemic brain.Experimental & molecular medicine · 2023Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulation of iron metabolism and innate immunity are tightly interlinked. The acute phase response to infection and inflammation induces alterations in iron homeostasis that reduce iron supplies to pathogens. The iron hormone hepcidin is activated by such stimuli causing degradation of the iron exporter ferroportin and reduced iron release from macrophages, suggesting that hepcidin is the crucial effector of inflammatory hypoferremia. Here, we report the discovery of an acute inflammatory condition that is mediated by Toll-like receptors 2 and 6 (TLR2 and TLR6) and which induces hypoferremia in mice injected with TLR ligands. Stimulation of TLR2/TLR6 triggers profound decreases in ferroportin messenger RNA and protein expression in bone marrow-derived macrophages, liver, and spleen of mice without changing hepcidin expression. Furthermore, C326S ferroportin mutant mice with a disrupted hepcidin/ferroportin regulatory circuitry respond to injection of the TLR2/6 ligands FSL1 or PAM3CSK4 by ferroportin downregulation and a reduction of serum iron levels. Our findings challenge the prevailing role of hepcidin in hypoferremia and suggest that rapid hepcidin-independent ferroportin downregulation in the major sites of iron recycling may represent a first-line response to restrict iron access for numerous pathogens.
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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.