ArticleNature medicine2015
The TAM receptor Mertk protects against neuroinvasive viral infection by maintaining blood-brain barrier integrity.
Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
99 citing papers in PubMed, 1 synthesis or guideline pooled it, 154 citations in OpenAlex.
- The Multifaceted Roles of TAM Receptors during Viral Infection.Virologica Sinica · 2021Pooled it
- Endothelial MerTK impairment promotes cardiac dysfunction in the condition of high fat diet.Redox biology · 2026Article
- Genetic mechanisms underlying host susceptibility to central nervous system viral infections.Current opinion in infectious diseases · 2026Review
- TYRO3, AXL, MERTK and Their Ligands in Brain Metastases From Colorectal Cancers.Cancer medicine · 2026Article
- Suppression of cardiac allograft vasculopathy by a macrophage efferocytosis receptor.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- Neuroinflammation and blood-brain barrier disruption in Japanese encephalitis virus infection: mechanisms, therapeutic targets, and intervention strategies.Archives of pharmacal research · 2026Review
- Pathogenic breaches: how viruses compromise blood-tissue barriers.Tissue barriers · 2026Review
- An Updated Review of Potential Drug Targets for Japanese Encephalitis.Central nervous system agents in medicinal chemistry · 2026Review
- PROS1/AXL signaling protects mice from lethal influenza infection by inducing M2 macrophage polarization.Acta biochimica et biophysica Sinica · 2025Article
- Review
- Chronic social defeat stress induces meningeal neutrophilia via type I interferon signaling in male mice.Nature communications · 2025Article
- NETs activate the GAS6-AXL-NLRP3 axis in macrophages to drive morphine tolerance.Cell communication and signaling : CCS · 2025Article
- Bystander neuronal progenitors in forebrain organoids promote protective antiviral responses.Journal of neuroinflammation · 2025Article
- The roles of microglia and astrocytes in neuroinflammation of Alzheimer's disease.Frontiers in neuroscience · 2025Review
- Single-cell transcriptomics of vascularized human brain organoids decipher lineage-specific stress adaptation in fetal hypoxia-reoxygenation injury.Theranostics · 2025Article
- STAMBPL1/TRIM21 Balances AXL Stability Impacting Mesenchymal Phenotype and Immune Response in KIRC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- TAM receptors mediate the Fpr2-driven pain resolution and fibrinolysis after nerve injury.Acta neuropathologica · 2024Article
- Neuropsychiatric Burden of SARS-CoV-2: A Review of Its Physiopathology, Underlying Mechanisms, and Management Strategies.Viruses · 2024Review
- GAS6 as a potential target to alleviate neuroinflammation during Japanese encephalitis in mouse models.Journal of neuroinflammation · 2024Article
- The protective role of Mertk in JEV-induced encephalitis by maintaining the integrity of blood-brain barrier.Virology journal · 2024Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The TAM receptors Tyro3, Axl and Mertk are receptor tyrosine kinases that dampen host innate immune responses following engagement with their ligands Gas6 and Protein S, which recognize phosphatidylserine on apoptotic cells. In a form of apoptotic mimicry, many enveloped viruses display phosphatidylserine on the outer leaflet of their membranes, enabling TAM receptor activation and downregulation of antiviral responses. Accordingly, we hypothesized that a deficiency of TAM receptors would enhance antiviral responses and protect against viral infection. Unexpectedly, mice lacking Mertk and/or Axl, but not Tyro3, exhibited greater vulnerability to infection with neuroinvasive West Nile and La Crosse encephalitis viruses. This phenotype was associated with increased blood-brain barrier permeability, which enhanced virus entry into and infection of the brain. Activation of Mertk synergized with interferon-β to tighten cell junctions and prevent virus transit across brain microvascular endothelial cells. Because TAM receptors restrict pathogenesis of neuroinvasive viruses, these findings have implications for TAM antagonists that are currently in clinical development.
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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.