ArticleCell reports2020
Counter Regulation of Spic by NF-κB and STAT Signaling Controls Inflammation and Iron Metabolism in Macrophages.
Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Therapeutic Effects of Natural Products on Liver Cancer and Their Potential Mechanisms.Nutrients · 2024Pooled it
- Molecular Mechanism Underlying IBRV-Induced Ferroptosis in MDBK Cells via the NFKB1-SLC39A8 Axis.Animals : an open access journal from MDPI · 2026Article
- An Integrated Multi-omics Single Cell Atlas of the Human RPE and Choroid.bioRxiv : the preprint server for biology · 2026Article
- SPIC-dependent erythrophagocytic macrophages drive granuloma formation and pathogen persistence during intracellular bacterial infection.bioRxiv : the preprint server for biology · 2026Article
- Single-nucleus epigenomic dysregulation unmasks genetic risk-associated neurodegenerative glia states.Nature communications · 2026Article
- The Emerging Role of Transcription Factor Spi-C in Macrophage Biology and Inflammatory Pathogenesis.International journal of molecular sciences · 2026Review
- Article
- Loss of NR2F6 Protects from Salmonella Typhimurium Infection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- TNFα signaling restores steady-state hematopoiesis in a TNFαKO mouse model of anemia of inflammation.Blood · 2025Article
- Iron-Immune Crosstalk at the Maternal-Fetal Interface: Emerging Mechanisms in the Pathogenesis of Preeclampsia.Antioxidants (Basel, Switzerland) · 2025Review
- Understanding the role of iron/heme metabolism in the anti‑inflammatory effects of natural sulfur molecules against lipopolysaccharide‑induced inflammation.Molecular medicine reports · 2025Article
- HFE-Related Hemochromatosis May Be a Primary Kupffer Cell Disease.Biomedicines · 2025Review
- Burn injury-induced G-CSF secretion reduces spic+ erythroblastic island macrophages in the bone marrow and impairs medullary erythropoiesis.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Multiarm-Assisted Design of Dendron-like Degradable Ionizable Lipids Facilitates Systemic mRNA Delivery to the Spleen.Journal of the American Chemical Society · 2025Article
- Article
- Iron, Hepcidin, and Immunity.Advances in experimental medicine and biology · 2025Review
- Integrated Single-Cell Analysis Revealed Novel Subpopulations of Foamy Macrophages in Human Atherosclerotic Plaques.Biomolecules · 2024Article
- The frequency of CD38Nature communications · 2024Article
- The Protective Role of Interleukin-37 in Cardiovascular Diseases through Ferroptosis Modulation.International journal of molecular sciences · 2024Review
- CD38+ Alveolar macrophages mediate early control of M. tuberculosis proliferation in the lung.Research square · 2024Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
Activated macrophages must carefully calibrate their inflammatory responses to balance efficient pathogen control with inflammation-mediated tissue damage, but the molecular underpinnings of this "balancing act" remain unclear. Using genetically engineered mouse models and primary macrophage cultures, we show that Toll-like receptor (TLR) signaling induces the expression of the transcription factor Spic selectively in patrolling monocytes and tissue macrophages by a nuclear factor κB (NF-κB)-dependent mechanism. Functionally, Spic downregulates pro-inflammatory cytokines and promotes iron efflux by regulating ferroportin expression in activated macrophages. Notably, interferon-gamma blocks Spic expression in a STAT1-dependent manner. High levels of interferon-gamma are indicative of ongoing infection, and in its absence, activated macrophages appear to engage a "default" Spic-dependent anti-inflammatory pathway. We also provide evidence for the engagement of this pathway in sterile inflammation. Taken together, our findings uncover a pathway wherein counter-regulation of Spic by NF-κB and STATs attune inflammatory responses and iron metabolism in macrophages.
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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.