ArticleCell death & disease2021
Ligand-dependent kinase activity of MERTK drives efferocytosis in human iPSC-derived macrophages.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Neutrophil-integrated syncytial CAR macrophage for cancer immunotherapy.Nature immunology · 2026Article
- S100A8/S100A9 released by CD11bExperimental & molecular medicine · 2026Article
- Dynamic remodeling of the pancreas immune landscape in obesity.Nature communications · 2026Article
- Macrophage efferocytosis in cardiovascular disease: mechanisms and therapeutic implications.ImmunoHorizons · 2026Review
- The postpartum uterus reveals compartment-specific remodeling processes with distinct immune signatures.Frontiers in immunology · 2026Article
- TAM-targeted nanomedicine in cancer: biological basis, therapeutic strategies, and translational perspectives.Theranostics · 2026Review
- MerTK Inhibition Aggravates Pancreatic Inflammation and Structural Damage via the NF-κB Pathway in an in vivo Type 2 Diabetic Rat Model.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Article
- Mechanistic Insights intoEndocrine, metabolic & immune disorders drug targets · 2026Article
- Single-Cell Insights Into Macrophage Subtypes in Pulmonary Infections.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Impaired Macrophage Efferocytosis: Shared Mechanisms and Therapeutic Implications in Immune-Mediated Inflammatory Diseases.Journal of inflammation research · 2026Review
- Dysregulated Resolution of Inflammation After Respiratory Viral Infections: Molecular Pathways Linking Neuroinflammation to Post-Viral Neuropathic Pain-A Narrative Review.International journal of molecular sciences · 2025Review
- Efferocytosis by Macrophages Attenuates Inflammatory Responses Following Ultraviolet B-Induced Apoptosis in Corneal Stromal Cells.Investigative ophthalmology & visual science · 2025Article
- Integrated single-cell transcriptomic map of pig kidney cells across various periods and anatomical sites.Zoological research · 2025Article
- ADAM8 in macrophages exacerbates sepsis-induced cardiomyopathy by impeding efferocytosis.Frontiers in immunology · 2025Article
- Gas6 induces AIM to suppress acute lung injury in mice by inhibiting NLRP3 inflammasome activation and inducing autophagy.Frontiers in immunology · 2025Article
- Article
- Review
- Gas6 and Protein S Ligands Cooperate to Regulate MerTK Rhythmic Activity Required for Circadian Retinal Phagocytosis.International journal of molecular sciences · 2024Article
- ACK1 and BRK non-receptor tyrosine kinase deficiencies are associated with familial systemic lupus and involved in efferocytosis.medRxiv : the preprint server for health sciences · 2024Article
- In the Eyes of the Beholder-NewInternational journal of molecular sciences · 2024Review
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Authors and funding
20 authors at 3 institutions in 3 countries.
Funding
Abstract
Removal of apoptotic cells by phagocytes (also called efferocytosis) is a crucial process for tissue homeostasis. Professional phagocytes express a plethora of surface receptors enabling them to sense and engulf apoptotic cells, thus avoiding persistence of dead cells and cellular debris and their consequent effects. Dysregulation of efferocytosis is thought to lead to secondary necrosis and associated inflammation and immune activation. Efferocytosis in primarily murine macrophages and dendritic cells has been shown to require TAM RTKs, with MERTK and AXL being critical for clearance of apoptotic cells. The functional role of human orthologs, especially the exact contribution of each individual receptor is less well studied. Here we show that human macrophages differentiated in vitro from iPSC-derived precursor cells express both AXL and MERTK and engulf apoptotic cells. TAM RTK agonism by the natural ligand growth-arrest specific 6 (GAS6) significantly enhanced such efferocytosis. Using a newly-developed mouse model of kinase-dead MERTK, we demonstrate that MERTK kinase activity is essential for efferocytosis in peritoneal macrophages in vivo. Moreover, human iPSC-derived macrophages treated in vitro with blocking antibodies or small molecule inhibitors recapitulated this observation. Hence, our results highlight a conserved MERTK function between mice and humans, and the critical role of its kinase activity in homeostatic efferocytosis.
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