ArticleScience immunology2021
Mitochondrial C5aR1 activity in macrophages controls IL-1β production underlying sterile inflammation.
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Article in Science immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
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110citing papers in PubMed
6.8field-weighted citation impact, top 2% of its field
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Who cites it
110 citing papers in PubMed, 140 citations in OpenAlex.
- Monocyte Activation Drives Atrial Fibrillation in Hypertension.Cardiovascular drugs and therapy · 2026Article
- Complement Activation by Post-Translationally Modified Proteins: Links to Chronic Inflammation and Autoimmunity.Immunological reviews · 2026Review
- Innate immunity: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Inflammation in atherosclerosis: Drivers, mechanisms and therapies.Acta pharmaceutica Sinica. B · 2026Review
- Deletion of decay-accelerating factor in kidney tubular cells mitigates kidney fibrosis in aristolochic acid nephropathy.American journal of physiology. Renal physiology · 2026Article
- Reprogramming macrophage metabolism for cardiovascular therapy: From molecular pathways to precision nanomedicine.Materials today. Bio · 2026Review
- What's your name, immune cell?Nature methods · 2026Article
- Mitochondria: The Crossroads of Complement Activation and Kidney Injury Progression.International journal of molecular sciences · 2026Review
- Metabolic Reprogramming-Driven Cardiovascular Immune Damage: From Glyco-Lipotoxicity and Epigenetic Memory to Multidimensional Cross-Organ Communication Networks.International journal of molecular sciences · 2026Review
- Effect of C5a Receptor Antagonist on the Osteogenic Differentiation of Dental Pulp Stem Cells.Clinical and experimental dental research · 2026Article
- Novel interactions between the C5-C5aR1 Axis and IF1: Implications for kidney mitochondrial physiology and ischemia-reperfusion injury.Physiological reports · 2026Article
- Single-cell transcriptomics and machine learning identify RNF144B and C5AR1 as immune-related molecular signatures and therapeutic targets in myocardial infarction.Genes & genomics · 2026Article
- Targeting C5AR1 disrupts complement-driven G0-phase maintenance and overcomes metabolic drug resistance in glioma.Journal of translational medicine · 2026Article
- Cytokines at the Crossroads of Mitochondrial Dysfunction and Inflammation in Colorectal Cancer: Implications for Postoperative Complications.Molecular diagnosis & therapy · 2026Review
- Article
- Complement Anaphylatoxin C5a-Induced Mouse Lymphatic Functions Modulate Interactions Between Endothelial Cells and T Lymphocytes.Immune network · 2026Article
- C/EBP-β-regulated complement hyperactivation in spleen of SFTSV-infected mice: A clue to targeted complement therapy.PLoS pathogens · 2026Article
- C5aR1 and cGAS/STING and their possible involvement in radiosensitivity of colorectal cancer.iScience · 2026Review
- Complement system in cancer: friend or foe of immunotherapy.Journal for immunotherapy of cancer · 2026Review
- Lipid metabolism in homeostasis and disease.Signal transduction and targeted therapy · 2026Review
50 more citing papers are in PubMed but not listed here.
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Authors and funding
37 authors at 10 institutions in 6 countries.
Nathalie NiyonzimaCenter of Molecular Inflammation Research (CEMIR), Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.ORCID 0000-0001-8094-3073
Jubayer RahmanComplement and Inflammation Research Section (CIRS), National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Natalia KunzComplement and Inflammation Research Section (CIRS), National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.ORCID 0000-0001-6583-360X
Erin E WestComplement and Inflammation Research Section (CIRS), National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.ORCID 0000-0002-7103-8394
Tilo FreiwaldImmunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD 20892, USA.ORCID 0000-0002-4759-717X
Jigar V DesaiFungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-8823-0796
Nicolas S MerleComplement and Inflammation Research Section (CIRS), National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Alexandre GidonCenter of Molecular Inflammation Research (CEMIR), Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Bjørnar SporsheimCenter of Molecular Inflammation Research (CEMIR), Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.ORCID 0000-0001-8304-9974
Michail S LionakisFungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0003-4994-9500
Kristin EvensenDepartment of Neurology, Vestre Viken, Drammen Hospital, Drammen, Norway.ORCID 0000-0002-7378-485X
Beate LindbergDepartment of Cardiothoracic Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway.ORCID 0000-0003-0956-8826
Karolina SkagenDepartment of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Mona SkjellandDepartment of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.ORCID 0000-0001-7950-4882
Parul SinghComplement and Inflammation Research Section (CIRS), National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Markus HaugCenter of Molecular Inflammation Research (CEMIR), Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.ORCID 0000-0001-6023-7972
Marieta M RusevaBG2, Adaptive Immunity Research Unit, GlaxoSmithKline, Stevenage, UK.
Martin KolevBG2, Adaptive Immunity Research Unit, GlaxoSmithKline, Stevenage, UK.
Jack BibbyComplement and Inflammation Research Section (CIRS), National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Olivia MarshallDiscovery DMPK Bioanalysis Unit, GlaxoSmithKline, Stevenage, UK.ORCID 0000-0003-3503-0413
Brett O'BrienDiscovery DMPK Bioanalysis Unit, GlaxoSmithKline, Stevenage, UK.ORCID 0000-0003-2997-3669
Nigel DeeksDiscovery DMPK Bioanalysis Unit, GlaxoSmithKline, Stevenage, UK.
Behdad AfzaliImmunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD 20892, USA.ORCID 0000-0003-2968-1156
Richard J ClarkSchool of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia.ORCID 0000-0002-6807-5426
Trent M WoodruffSchool of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia.ORCID 0000-0003-1382-911X
Milton PryorLipoprotein Metabolism Section, Cardiopulmonary Branch, NHLBI, NIH, Bethesda, MD 20892, USA.
Zhi-Hong YangLipoprotein Metabolism Section, Cardiopulmonary Branch, NHLBI, NIH, Bethesda, MD 20892, USA.
Alan T RemaleyLipoprotein Metabolism Section, Cardiopulmonary Branch, NHLBI, NIH, Bethesda, MD 20892, USA.ORCID 0000-0003-2473-5549
Tom E MollnesCenter of Molecular Inflammation Research (CEMIR), Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.ORCID 0000-0002-5785-802X
Stephen M HewittLaboratory of Pathology, National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USA.ORCID 0000-0001-8283-1788
Bingyu YanDepartments of Biochemistry and Computer Science, Purdue University, West Lafayette, IN 47907, USA.ORCID 0000-0003-4429-8200
Majid KazemianDepartments of Biochemistry and Computer Science, Purdue University, West Lafayette, IN 47907, USA.ORCID 0000-0001-7080-8820
Máté G KissDepartment of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.ORCID 0000-0002-9215-8328
Christoph J BinderDepartment of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.ORCID 0000-0001-8313-7050
Bente HalvorsenInstitute of Clinical Medicine, University of Oslo, Oslo, Norway.ORCID 0000-0002-6529-6485
Terje EspevikCenter of Molecular Inflammation Research (CEMIR), Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.ORCID 0000-0003-0354-5068
Claudia KemperComplement and Inflammation Research Section (CIRS), National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.ORCID 0000-0003-4196-1417
National Institutes of Health · USGlaxoSmithKline (United Kingdom) · GBNorwegian University of Science and Technology · NOOslo University Hospital · NOAustrian Academy of Sciences · ATNational Institute of Diabetes and Digestive and Kidney Diseases · USPurdue University West Lafayette · USThe University of Queensland · AUDrammen Hospital · NONational Cancer Institute · US
Funding
Unravelling immunoregulatory circuits of tissue inflammationZIADK075149 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI AFZALI, BEHDAD · 2019 to 2025
$19.3MJoint submission for administrative supplement proposal: HIPAA aligned storage and computing solutionR35GM138283 · NIGMS · PURDUE UNIVERSITY · PI KAZEMIAN, MAJID · 2020 to 2024
$2.0MExpression, regulation, and role of enhancer RNAs in T helper cellsK22HL125593 · NHLBI · PURDUE UNIVERSITY · PI KAZEMIAN, MAJID · 2017 to 2019
$747kDepartment of HealthNHLBI NIH HHS K22 HL125593NIAID NIH HHS K99 AI141622NIGMS NIH HHS R35 GM138283Wellcome Trust
Abstract
While serum-circulating complement destroys invading pathogens, intracellularly active complement, termed the “complosome,” functions as a vital orchestrator of cell-metabolic events underlying T cell effector responses. Whether intracellular complement is also nonredundant for the activity of myeloid immune cells is currently unknown. Here, we show that monocytes and macrophages constitutively express complement component (C) 5 and generate autocrine C5a via formation of an intracellular C5 convertase. Cholesterol crystal sensing by macrophages induced C5aR1 signaling on mitochondrial membranes, which shifted ATP production via reverse electron chain flux toward reactive oxygen species generation and anaerobic glycolysis to favor IL-1β production, both at the transcriptional level and processing of pro–IL-1β. Consequently, atherosclerosis-prone mice lacking macrophage-specific
Indexed as
AnimalsCell LineHumansInflammationInterleukin-1betaMacrophagesMiceMice, Inbred C57BLMice, KnockoutReceptor, Anaphylatoxin C5aC5ar1 protein, mouseIL1B protein, mouseInterleukin-1betaReceptor, Anaphylatoxin C5a
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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.