ArticleThe Journal of clinical investigation2020
Hemolysis transforms liver macrophages into antiinflammatory erythrophagocytes.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 71 citations in OpenAlex.
- Kupffer cells are key mediators of antigen-specific immune tolerance by peptide-coupled red blood cells.Science advances · 2026Article
- Haemolytic injury and cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Sickle cell disease-associated pulmonary hypertension: an integrated framework linking pathologies, mechanisms, and clinical phenotypes.EBioMedicine · 2026Review
- SPIC-dependent erythrophagocytic macrophages drive granuloma formation and pathogen persistence during intracellular bacterial infection.bioRxiv : the preprint server for biology · 2026Article
- Hepatitis C Virus: An Overview of Its Chronic Impact on Liver Function, Metabolic Dysregulation, Inflammatory-Oxidative Pathogenesis and Epigenetic Memory.International journal of molecular sciences · 2026Review
- Article
- Loss of energy homeostasis contributes to hepatic damage development in sickle cell disease.Molecular metabolism · 2026Article
- An ontogeny-cytokine code determines macrophage response polarity and tumor outcomes.Communications biology · 2026Article
- Ubiquitination and degradation of CD47 enhances macrophage phagocytosis of hemolytic erythrocytes.iScience · 2026Article
- Erythrocytes as immunomodulators in trauma: orchestrating clearance pathways, inflammation, and organ injury.Frontiers in immunology · 2026Review
- One trigger, two fates: hemolysate shapes neutrophil extracellular traps (NETs) formation in a context-dependent manner.Frontiers in immunology · 2026Article
- Iron and the immune system.Nature reviews. Immunology · 2025Review
- Stress-NRF2 response axis polarizes tumor macrophages and undermines immunotherapy.Journal for immunotherapy of cancer · 2025Article
- Eryptosis in Liver Diseases: Contribution to Anemia and Hypercoagulation.Medical sciences (Basel, Switzerland) · 2025Review
- The Nrf2 Activator CDDO-Imidazole Suppresses Inflammation-Induced Red Blood Cell Alloimmunization.Antioxidants (Basel, Switzerland) · 2025Article
- Haptoglobin Attenuates Cerebrospinal Fluid Hemoglobin-Induced Neurological Deterioration in Sheep.Translational stroke research · 2025Article
- CDDO-Imidazole regulates RBC alloimmunization to the KEL antigen by activating Nrf2.bioRxiv : the preprint server for biology · 2025Article
- Pro-Oxidative and Inflammatory Actions of Extracellular Hemoglobin and Heme: Molecular Events and Implications for Alzheimer's and Parkinson Disease.Biomolecules & therapeutics · 2025Review
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- The Molecular Determinants of Erythrocyte Removal Impact the Development of Metabolic Dysfunction-Associated Steatohepatitis.Endocrine, metabolic & immune disorders drug targets · 2025Review
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During hemolysis, macrophages in the liver phagocytose damaged erythrocytes to prevent the toxic effects of cell-free hemoglobin and heme. It remains unclear how this homeostatic process modulates phagocyte functions in inflammatory diseases. Using a genetic mouse model of spherocytosis and single-cell RNA sequencing, we found that erythrophagocytosis skewed liver macrophages into an antiinflammatory phenotype that we defined as MarcohiHmoxhiMHC class IIlo erythrophagocytes. This phenotype transformation profoundly mitigated disease expression in a model of an anti-CD40-induced hyperinflammatory syndrome with necrotic hepatitis and in a nonalcoholic steatohepatitis model, representing 2 macrophage-driven sterile inflammatory diseases. We reproduced the antiinflammatory erythrophagocyte transformation in vitro by heme exposure of mouse and human macrophages, yielding a distinctive transcriptional signature that segregated heme-polarized from M1- and M2-polarized cells. Mapping transposase-accessible chromatin in single cells by sequencing defined the transcription factor NFE2L2/NRF2 as a critical driver of erythrophagocytes, and Nfe2l2/Nrf2 deficiency restored heme-suppressed inflammation. Our findings point to a pathway that regulates macrophage functions to link erythrocyte homeostasis with innate immunity.
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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.