ArticleImmunity2020
Diapedesis-Induced Integrin Signaling via LFA-1 Facilitates Tissue Immunity by Inducing Intrinsic Complement C3 Expression in Immune Cells.
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Article in Immunity, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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66citing papers in PubMed
4.5field-weighted citation impact, top 4% of its field
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Who cites it
66 citing papers in PubMed, 99 citations in OpenAlex.
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- Type 2 and type 1 diabetes have opposing effects on the systemic murine complement alternative pathway.iScience · 2026Article
- Mechanistic insight into complement C3 regulation during chronic HBV infection: effect on viral persistence and host immune response.Journal of biomedical science · 2026Article
- The Complosome: An Emerging Intracellular Complement Network in Cancer Development and Therapy.International journal of molecular sciences · 2026Review
- Beta-cell-specific C3 deficiency exacerbates metabolic dysregulation and insulin resistance in obesity.Molecular metabolism · 2026Article
- Comprehensive cancer analysis reveals CFH as an immune-related and prognostic marker.BMC cancer · 2025Article
- The complement cascade in Alzheimer's disease: modern implications of an ancient immune protagonist.Molecular neurodegeneration · 2025Review
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- Complement factor D (adipsin) mediates pressure-pain hypersensitivity post destabilization of medial meniscus injury.Arthritis research & therapy · 2025Article
- Comparative single-cell and spatial profiling of anti-SSA-positive and anti-centromere-positive Sjögren's disease reveals common and distinct immune activation and fibroblast-mediated inflammation.Nature communications · 2025Article
- Inside job: Roles of intracellular C3.The Journal of allergy and clinical immunology · 2025Review
- Global C3 lowering in adulthood protects against hippocampal dysfunction and cognitive impairment in aged mice.Research square · 2025Article
- The secret life of complement: challenges and opportunities in exploring functions of the complosome in disease.The Journal of clinical investigation · 2025Review
- A CD4Immunity · 2025Article
- Complement's involvement in allergic Th2 immunity: a cross-barrier perspective.The Journal of clinical investigation · 2025Review
- Fibroblast derived C3 promotes the progression of experimental periodontitis through macrophage M1 polarization and osteoclast differentiation.International journal of oral science · 2025Article
- Myeloid lineage C3 induces reactive gliosis and neuronal stress during CNS inflammation.Nature communications · 2025Article
- An intracellular complement system drives metabolic and proinflammatory reprogramming of vascular fibroblasts in pulmonary hypertension.JCI insight · 2025Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 11 institutions in 4 countries.
Martin KolevComplement and Inflammation Research Section (CIRS), National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Erin E WestComplement 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.
Daniel ChaussImmunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD 20892, USA.
E Ashley MosemanViral Immunology & Intravital Imaging Section, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, MD 20892, USA.
Jubayer RahmanViral Immunology & Intravital Imaging Section, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, MD 20892, USA.
Tilo FreiwaldImmunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD 20892, USA.
Maria L BalmerDepartment of Biomedicine, Immunobiology, University Hospital and University of Basel, Basel 4031, Switzerland.
Jonas LötscherDepartment of Biomedicine, Immunobiology, University Hospital and University of Basel, Basel 4031, Switzerland.
Sarah DimeloeDepartment of Biomedicine, Immunobiology, University Hospital and University of Basel, Basel 4031, Switzerland; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.
Elizabeth C RosserInfection, Immunity, Inflammation Programme, University College London (UCL) Great Ormond Street Institute of Child Health, London WC1N 1EH, UK; Arthritis Research UK Centre for Adolescent Rheumatology at UCL, UCHL and GOSH, London WC1N 1EH, UK.
Lucy R WedderburnInfection, Immunity, Inflammation Programme, University College London (UCL) Great Ormond Street Institute of Child Health, London WC1N 1EH, UK; Arthritis Research UK Centre for Adolescent Rheumatology at UCL, UCHL and GOSH, London WC1N 1EH, UK; National Institute for Health Research (NIHR) Biomedical Research Centre at Great Ormond Street NHS Foundation Trust, London WC1N 1EH, UK.
Katrin D Mayer-BarberInflammation and Innate Immunity Unit, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892, USA.
Andrea BohrerInflammation and Innate Immunity Unit, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892, USA.
Paul LavenderSchool of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London SE1 9RT, UK.
Andrew CopeSchool of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London SE1 9RT, UK.
Luopin WangDepartments of Biochemistry and Computer Science, Purdue University, West Lafayette, IN 47907, USA.
Mariana J KaplanSystemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Disease (NIAMS), NIH, Bethesda, MD 20892, USA.
Niki M MoutsopoulosOral Immunity and Inflammation Unit, National Institute of Dental and Craniofacial Research (NIDCR), NIH, Bethesda, MD 20892, USA.
Dorian McGavernViral Immunology & Intravital Imaging Section, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, MD 20892, USA.
Steven M HollandLaboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD 20892, USA.
Christoph HessDepartment of Biomedicine, Immunobiology, University Hospital and University of Basel, Basel 4031, Switzerland; Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK.
Majid KazemianDepartments of Biochemistry and Computer Science, Purdue University, West Lafayette, IN 47907, USA. Electronic address: kazemian@purdue.edu.
Behdad AfzaliImmunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD 20892, USA. Electronic address: behdad.afzali@nih.gov.
Claudia KemperComplement and Inflammation Research Section (CIRS), National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA; School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London SE1 9RT, UK; Institute for Systemic Inflammation Research, University of Lübeck, Lübeck 23562, Germany. Electronic address: claudia.kemper@nih.gov.
National Institutes of Health · USUniversity of Basel · CHNational Institute of Diabetes and Digestive and Kidney Diseases · USNational Institute of Neurological Disorders and Stroke · USKing's College London · GBNational Institute of Allergy and Infectious Diseases · USPurdue University West Lafayette · USArthritis UK · GBGreat Ormond Street Hospital for Children NHS Foundation Trust · GBNational Institute of Arthritis and Musculoskeletal and Skin Diseases · USNational Institute of Dental and Craniofacial Research · US
Funding
Systemic AutoimmunityZIAAR041199 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI KAPLAN, MARIANA · 2014 to 2025
$32.5MGenes And Gene Products As ImmunoadjuvantsZIAAI000647 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI HOLLAND, STEVEN · 2009 to 2025
$22.6MTransgenic Animal Models Of Human Immune DefectsZIAAI000646 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI HOLLAND, STEVEN · 2009 to 2025
$22.2MUnravelling immunoregulatory circuits of tissue inflammationZIADK075149 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI AFZALI, BEHDAD · 2019 to 2025
$19.3MThe role of the intracellular complement system - the complosome - in Th1 biologyZIAHL006223 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI KEMPER, CLAUDIA · 2017 to 2025
$16.9MInnate inflammatory responses during pulmonary infectionsZIAAI001207 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MAYER-BARBER, KATRIN · 2015 to 2025
$13.6MOral Microbial and Immunological Characterization of Patients with Immune DysfunZIADE000732 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI MOUTSOPOULOS, NIKI · 2010 to 2024
$13.2MThe role of the intracellular complement system - the complosome - in monocytesZIAHL006222 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI KEMPER, CLAUDIA · 2017 to 2025
$3.2MA New Therapy for Bowel Ischemia-Reperfusion InjuryR44DK075149 · NIDDK · THERASOURCE, LLC · PI JACOB, ASHA · 2010 to 2012
$1.2MExpression, regulation, and role of enhancer RNAs in T helper cellsK22HL125593 · NHLBI · PURDUE UNIVERSITY · PI KAZEMIAN, MAJID · 2017 to 2019
$747kNew Therapy for Bowel Ischemia-Reperfusion InjuryR43DK075149 · NIDDK · THERASOURCE, LLC · PI WU, RONGQIAN · 2006 to 2007
$288kDepartment of HealthIntramural NIH HHS ZIA DK075149Intramural NIH HHS ZIA HL006222Intramural NIH HHS ZIA HL006223Medical Research Council MR/J006742/1Medical Research Council MR/M004600/1NHLBI NIH HHS K22 HL125593NIDDK NIH HHS R43 DK075149NIDDK NIH HHS R44 DK075149Versus Arthritis 21226Wellcome TrustWellcome Trust 097261/Z/11/ZWellcome Trust 102932/Z/13/Z
Abstract
Intrinsic complement C3 activity is integral to human T helper type 1 (Th1) and cytotoxic T cell responses. Increased or decreased intracellular C3 results in autoimmunity and infections, respectively. The mechanisms regulating intracellular C3 expression remain undefined. We identified complement, including C3, as among the most significantly enriched biological pathway in tissue-occupying cells. We generated C3-reporter mice and confirmed that C3 expression was a defining feature of tissue-immune cells, including T cells and monocytes, occurred during transendothelial diapedesis, and depended on integrin lymphocyte-function-associated antigen 1 (LFA-1) signals. Immune cells from patients with leukocyte adhesion deficiency type 1 (LAD-1) had reduced C3 transcripts and diminished effector activities, which could be rescued proportionally by intracellular C3 provision. Conversely, increased C3 expression by T cells from arthritis patients correlated with disease severity. Our study defines integrins as key controllers of intracellular complement, demonstrates that perturbations in the LFA-1-C3-axis contribute to primary immunodeficiency, and identifies intracellular C3 as biomarker of severity in autoimmunity.
Indexed as
AdultAgedAnimalsArthritis, RheumatoidChildChild, PreschoolComplement C3FemaleHumansIntegrinsLymphocyte Function-Associated Antigen-1LymphocytesMaleMice, Inbred C57BLMiddle AgedMonocytesComplement C3IntegrinsLymphocyte Function-Associated Antigen-1autoimmunitybiomarkercomplosomeintegrinsintracellular complementLAD-1LFA-1lymphocyte adhesion deficiency type 1metabolismT cellsTh1 cells
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