ArticleNature communications2023
Constitutively active Lyn kinase causes a cutaneous small vessel vasculitis and liver fibrosis syndrome.
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Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 29 citations in OpenAlex.
- The Src-Family Kinases Hck, Fgr and Lyn Drive Immune Complex-Mediated Glomerulonephritis Through the Syk Tyrosine Kinase.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The protein tyrosine phosphatase CD45 promotes PMN transepithelial migration, antimicrobial function, and colonic mucosal repair.JCI insight · 2026Article
- Screening of diagnostic biomarkers for taurine metabolism-related genes in lupus nephritis and analysis of immune infiltration.International urology and nephrology · 2026Article
- Decoding variants of uncertain significance in systemic autoinflammatory diseases.Nature reviews. Rheumatology · 2026Review
- Expanding the Spectrum of Src-Family Kinase-Related Autoinflammatory Diseases: Monogenic Vasculitis Caused By Germline Pathogenic Variants in HCK and FGR.Journal of clinical immunology · 2026Article
- Identifying ICAM-1 as a Therapeutic Target for Cytokine Storm in Human Macrophages Through Integrative Bioinformatics Approaches.Molecules (Basel, Switzerland) · 2026Article
- Lyn governs the establishment and maintenance of B cell anergy by suppressing PI3K signaling.Nature communications · 2026Article
- Unveiling the Immunopharmacological Mechanisms of Biejiajian Pills (BJJP) Underlying the Treatment of Hepatic Fibrosis: Insights From Network Pharmacology and Experimental Validation.Food science & nutrition · 2026Article
- Recent variant discoveries and emerging genetic mechanisms in autoinflammatory diseases.Frontiers in immunology · 2026Review
- Proteomic and Functional Comparison of Extracellular Vesicles from Wild-Type and Lyn-Deficient Stromal Cells.Advances in experimental medicine and biology · 2026Article
- Tracking inflammation status for improving patient prognosis: A review of current methods, unmet clinical needs and opportunities.Biotechnology advances · 2025Review
- The pathogenesis, clinical presentations and treatment of monogenic systemic vasculitis.Nature reviews. Rheumatology · 2025Review
- Altered maturation and activation state of circulating monocytes is associated with their enhanced recruitment in pulmonary arterial hypertension.Respiratory research · 2025Article
- Article
- Mapping the genetic landscape of immune-mediated disorders: potential implications for classification and therapeutic strategies.Frontiers in immunology · 2025Article
- Charting the Dynamic Trophoblast Plasma Membrane Identifies LYN As a Functional Regulator of Syncytialization.ACS chemical biology · 2024Article
- Autoinflammation in patients with leukocytic CBL loss of heterozygosity is caused by constitutive ERK-mediated monocyte activation.The Journal of clinical investigation · 2024Article
- Article
- Role of Sam68 as an adaptor protein in inflammatory signaling.Cellular and molecular life sciences : CMLS · 2024Review
- New genes, pathways and therapeutic targets in autoinflammatory diseases.Nature reviews. Rheumatology · 2024Article
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Authors and funding
54 authors at 12 institutions in 4 countries.
Adriana A de Jesus *Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-8966-8362
Guibin Chen *National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Dan Yang *National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Tomas BrdickaLaboratory of Leukocyte Signaling, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.ORCID 0000-0002-1560-4398
Natasha M RuthMedical University of South Carolina, Charleston, SC, USA.
David BenninDepartments of Pediatrics and Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, USA.
Dita CebecauerovaSecond Faculty of Medicine, Charles University/University Hospital Motol, Prague, Czech Republic.
Hana MalcovaSecond Faculty of Medicine, Charles University/University Hospital Motol, Prague, Czech Republic.
Helen FreemanRaigmore Hospital, Inverness, Scotland.ORCID 0000-0001-9181-1463
Neil MartinRoyal Hospital for Children, Glasgow, Scotland.
Karel SvojgrSecond Faculty of Medicine, Charles University/University Hospital Motol, Prague, Czech Republic.ORCID 0000-0003-1267-4072
Murray H PassoMedical University of South Carolina, Charleston, SC, USA.
Farzana BhuyanTranslational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Sara AlehashemiTranslational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Andre T RastegarTranslational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Katsiaryna UssTranslational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Lela KardavaLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Bernadette MarreroTranslational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Iris DuricLaboratory of Leukocyte Signaling, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.ORCID 0000-0002-5227-6522
Ebun OmoyinmiGreat Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Petra PeldovaSecond Faculty of Medicine, Charles University/University Hospital Motol, Prague, Czech Republic.
Chyi-Chia Richard LeeNational Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
David E KleinerNational Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Colleen M HadiganClinical Center, National Institutes of Health, Bethesda, MD, USA.
Stephen M HewittNational Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Stefania PittalugaNational Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-7688-1439
Carmelo Carmona-RiveraNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-7706-1464
Katherine R CalvoClinical Center, National Institutes of Health, Bethesda, MD, USA.
Nirali ShahNational Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-8474-9080
Miroslava BalascakovaSecond Faculty of Medicine, Charles University/University Hospital Motol, Prague, Czech Republic.
Danielle L FinkCollaborative Clinical Research Branch/Neutrophil Monitoring Laboratory, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA.
Radana KotalovaSecond Faculty of Medicine, Charles University/University Hospital Motol, Prague, Czech Republic.
Zuzana ParackovaSecond Faculty of Medicine, Charles University/University Hospital Motol, Prague, Czech Republic.ORCID 0000-0002-2398-532X
Lucie PeterkovaSecond Faculty of Medicine, Charles University/University Hospital Motol, Prague, Czech Republic.ORCID 0000-0003-3653-8358
Daniela KuzilkovaSecond Faculty of Medicine, Charles University/University Hospital Motol, Prague, Czech Republic.ORCID 0000-0001-8086-9790
Vit CamprSecond Faculty of Medicine, Charles University/University Hospital Motol, Prague, Czech Republic.
Lucie SramkovaSecond Faculty of Medicine, Charles University/University Hospital Motol, Prague, Czech Republic.
Angelique BiancottoSanofi Oncology, Vitry, France.ORCID 0000-0003-2271-009X
Stephen R BrooksNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-5592-5332
Cameron ManesYale University, New Haven, CT, USA.
Eric MeffreYale University, New Haven, CT, USA.ORCID 0000-0003-4326-0171
Rebecca L HarperNational Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-1465-7372
Hyesun KuehnClinical Center, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-2154-3966
Mariana J KaplanNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-2968-0815
Paul BroganGreat Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Sergio D RosenzweigClinical Center, National Institutes of Health, Bethesda, MD, USA.
Melinda MerchantAstraZeneca Research Based Biopharmaceutical Company, Waltham, MA, USA.
Zuoming DengNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Anna HuttenlocherDepartments of Pediatrics and Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, USA.
Susan L MoirLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-0163-6911
Douglas B KuhnsCollaborative Clinical Research Branch/Neutrophil Monitoring Laboratory, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA.ORCID 0000-0002-9971-0760
Manfred Boehm *National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Karolina Skvarova Kramarzova *Second Faculty of Medicine, Charles University/University Hospital Motol, Prague, Czech Republic.ORCID 0000-0003-4860-7453
Raphaela Goldbach-Mansky *Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. goldbacr@mail.nih.gov.ORCID 0000-0001-7865-5769
National Institutes of Health · USCharles University · CZNational Institutes of Health Clinical Center · USCzech Academy of Sciences, Institute of Molecular Genetics · CZGreat Ormond Street Hospital for Children NHS Foundation Trust · GBMedical University of South Carolina · USUniversity of Wisconsin–Madison · USYale University · USAstraZeneca (United States) · USRaigmore Hospital · GBRoyal Hospital for Children · GBSanofi (France) · FR
Funding
Systemic AutoimmunityZIAAR041199 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI KAPLAN, MARIANA · 2014 to 2025
$32.5MRole of B Lymphocytes In HIV Infection And PathogenesisZIAAI000825 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MOIR, SUSAN · 2009 to 2025
$24.5MVascular remodeling in patients with rare genetic disordersZIAHL006077 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI BOEHM, MANFRED · 2010 to 2025
$22.9MPathogenesis, and Outcome of Autoinflammatory Diseases, NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Stills-like Diseases, and other Undifferentiated Autoinflammatory DiseasesZIAAI001220 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI GOLDBACH-MANSKY, RAPHAELA · 2017 to 2025
$22.3MExperimental Pathology Laboratory (EPL)ZICBC011638 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HEWITT, STEPHEN · 2015 to 2025
$16.6MiPS-technology and patient specific disease modelsZIAHL006079 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI BOEHM, MANFRED · 2010 to 2025
$14.4MPostmortem PathologyZICBC010685 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KLEINER, DAVID ERWIN · 2009 to 2025
$14.3MApplying Bioinformatics to Research in Immune, Muscle, and Bone DiseasesZICAR041173 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI SUN, HONG-WEI · 2021 to 2025
$10.3MAbstract
Neutrophilic inflammation is a hallmark of many monogenic autoinflammatory diseases; pathomechanisms that regulate extravasation of damaging immune cells into surrounding tissues are poorly understood. Here we identified three unrelated boys with perinatal-onset of neutrophilic cutaneous small vessel vasculitis and systemic inflammation. Two patients developed liver fibrosis in their first year of life. Next-generation sequencing identified two de novo truncating variants in the Src-family tyrosine kinase, LYN, p.Y508*, p.Q507* and a de novo missense variant, p.Y508F, that result in constitutive activation of Lyn kinase. Functional studies revealed increased expression of ICAM-1 on induced patient-derived endothelial cells (iECs) and of β2-integrins on patient neutrophils that increase neutrophil adhesion and vascular transendothelial migration (TEM). Treatment with TNF inhibition improved systemic inflammation; and liver fibrosis resolved on treatment with the Src kinase inhibitor dasatinib. Our findings reveal a critical role for Lyn kinase in modulating inflammatory signals, regulating microvascular permeability and neutrophil recruitment, and in promoting hepatic fibrosis.
Indexed as
Endothelial Cellssrc-Family KinasesVasculitisDasatinibHumansInflammationNeutrophilsPhosphorylationDasatiniblyn protein-tyrosine kinasesrc-Family Kinases
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