ArticleClinical immunology (Orlando, Fla.)2016
Heightened cleavage of Axl receptor tyrosine kinase by ADAM metalloproteases may contribute to disease pathogenesis in SLE.
Article in Clinical immunology (Orlando, Fla.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 80 citations in OpenAlex.
- AXL at the nexus of therapeutic resistance, tumor vascularization, and immune evasion in cancer.iScience · 2026Review
- Sublytic pyroptosis blocks Schwann cell remyelination through caspase-1-mediated Tyro3 cleavage.Journal of neuroinflammation · 2026Article
- Therapeutic potential of TAM receptors in autoimmune diseases: insights from original studies.Oxford open immunology · 2026Review
- Potential Therapeutic Targets and Emerging Strategies to Promote Hematoma Resolution in Intracerebral Hemorrhage.Revista de neurologia · 2025Review
- From pathogenesis to therapeutic targeting: new insight into TAM receptors in rheumatoid arthritis.Cell & bioscience · 2025Review
- Proteolysis of TAM receptors in autoimmune diseases and cancer: what does it say to us?Cell death & disease · 2025Review
- Could Gas6/TAM Axis Provide Valuable Insights into the Pathogenesis of Systemic Sclerosis?Current issues in molecular biology · 2024Review
- A Disintegrin and metalloproteinase carves T cell abnormalities and pathogenesis in systemic lupus erythematosus.Clinical immunology (Orlando, Fla.) · 2024Review
- Efferocytosis: Current status and future prospects in the treatment of autoimmune diseases.Heliyon · 2024Review
- iRhom2 regulates ectodomain shedding and surface expression of the major histocompatibility complex (MHC) class I.Cellular and molecular life sciences : CMLS · 2024Article
- Axl and MerTK regulate synovial inflammation and are modulated by IL-6 inhibition in rheumatoid arthritis.Nature communications · 2024Article
- Peptidoglycan from Bacillus anthracis Inhibits Human Macrophage Efferocytosis in Part by Reducing Cell Surface Expression of MERTK and TIM-3.ImmunoHorizons · 2024Article
- GAS6/TAM Axis as Therapeutic Target in Liver Diseases.Seminars in liver disease · 2024Article
- Efferocytosis by macrophages in physiological and pathological conditions: regulatory pathways and molecular mechanisms.Frontiers in immunology · 2024Review
- Neutrophil-like pH-responsive pro-efferocytic nanoparticles improve neurological recovery by promoting erythrophagocytosis after intracerebral hemorrhage.Theranostics · 2024Article
- From MASH to HCC: the role of Gas6/TAM receptors.Frontiers in immunology · 2024Review
- Gas6/TAM Axis Involvement in Modulating Inflammation and Fibrosis in COVID-19 Patients.International journal of molecular sciences · 2023Review
- Altered expression of AXL receptor tyrosine kinase in gastrointestinal cancers: a promising therapeutic target.Frontiers in oncology · 2023Review
- The effect of combining PD-1 agonist and low-dose Interleukin-2 on treating systemic lupus erythematosus.Frontiers in immunology · 2023Review
- Elevated expression of TAM receptor tyrosine kinase in synovial fluid and synovial tissue of rheumatoid arthritis.Clinical and experimental immunology · 2022Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Systemic lupus erythematosus (SLE) is characterized by antibody-mediated chronic inflammation in the kidney, lung, skin, and other organs to cause inflammation and damage. Several inflammatory pathways are dysregulated in SLE, and understanding these pathways may improve diagnosis and treatment. In one such pathway, Axl tyrosine kinase receptor responds to Gas6 ligand to block inflammation in leukocytes. A soluble form of the Axl receptor ectodomain (sAxl) is elevated in serum from patients with SLE and lupus-prone mice. We hypothesized that sAxl in SLE serum originates from the surface of leukocytes and that the loss of leukocyte Axl contributes to the disease. We determined that macrophages and B cells are a source of sAxl in SLE and in lupus-prone mice. Shedding of the Axl ectodomain from the leukocytes of lupus-prone mice is mediated by the matrix metalloproteases ADAM10 and TACE (ADAM17). Loss of Axl from lupus-prone macrophages renders them unresponsive to Gas6-induced anti-inflammatory signaling in vitro. This phenotype is rescued by combined ADAM10/TACE inhibition. Mice with Axl-deficient macrophages develop worse disease than controls when challenged with anti-glomerular basement membrane (anti-GBM) sera in an induced model of nephritis. ADAM10 and TACE also mediate human SLE PBMC Axl cleavage. Collectively, these studies indicate that increased metalloprotease-mediated cleavage of leukocyte Axl may contribute to end organ disease in lupus. They further suggest dual ADAM10/TACE inhibition as a potential therapeutic modality in SLE.
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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.