ArticleScience advances2020
Cellular sensing of extracellular purine nucleosides triggers an innate IFN-β response.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
32 citing papers in PubMed, 43 citations in OpenAlex.
- Adenosine deaminase type 2 deficiency: From rare to common.Journal of human immunity · 2026Review
- Histone H3.3 ensures cell proliferation and genomic stability during myeloid cell development.iScience · 2026Article
- Worming out defence strategies: mechanisms of immunity through the lens of genetic screens in C. elegans.Heredity · 2026Review
- Sex Differences in Metabolite-Immune Circuits of Neuroinflammation.Immunological reviews · 2026Review
- Linoleoyl-lysophosphatidylcholine drives non-inflammatory apoptosis in neutrophils via lipid rafts.Frontiers in immunology · 2026Article
- Deoxyguanosine kinase deficiency couples purine metabolism to innate immune activation and lipid accumulation in hepatocytes.Frontiers in immunology · 2026Article
- Sex differences in tissue-specific immunity and immunology.Science (New York, N.Y.) · 2025Review
- Sex differences in adenosine deaminase activity associate with disparities in SARS-CoV-2 innate immunity.iScience · 2025Article
- Getting to know adenosine deaminase 2 deficiency inside and out.The Journal of allergy and clinical immunology · 2025Review
- Article
- Early-onset neutropenia and mixed phenotype in ADA2 deficiency: diagnostic and therapeutic challenges.Frontiers in immunology · 2025Article
- Emerging concepts and treatments in autoinflammatory interferonopathies and monogenic systemic lupus erythematosus.Nature reviews. Rheumatology · 2025Review
- Comparative genomics of Plasmodium yoelii nigeriensis N67 and N67C: genome-wide polymorphisms, differential gene expression, and drug resistance.BMC genomics · 2024Article
- Adenosine deaminase 2 regulates the activation of the toll-like receptor 9 in response to nucleic acids.Frontiers of medicine · 2024Article
- Human ADA2 Deficiency: Ten Years Later.Current allergy and asthma reports · 2024Review
- Linoleoyl-lysophosphatidylcholine suppresses immune-related adverse events due to immune checkpoint blockade.medRxiv : the preprint server for health sciences · 2024Article
- Similarities in the induction of the intracellular pathogen response in Caenorhabditis elegans and the type I interferon response in mammals.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- Inborn Errors of Purine Salvage and Catabolism.Metabolites · 2023Review
- Adenylosuccinic Acid: An Orphan Drug with Untapped Potential.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Low-dose arecoline regulates distinct core signaling pathways in oral submucous fibrosis and oral squamous cell carcinoma.BMC oral health · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Mechanisms linking immune sensing of DNA danger signals in the extracellular environment to innate pathways in the cytosol are poorly understood. Here, we identify a previously unidentified immune-metabolic axis by which cells respond to purine nucleosides and trigger a type I interferon-β (IFN-β) response. We find that depletion of ADA2, an ectoenzyme that catabolizes extracellular dAdo to dIno, or supplementation of dAdo or dIno stimulates IFN-β. Under conditions of reduced ADA2 enzyme activity, dAdo is transported into cells and undergoes catabolysis by the cytosolic isoenzyme ADA1, driving intracellular accumulation of dIno. dIno is a functional immunometabolite that interferes with the cellular methionine cycle by inhibiting SAM synthetase activity. Inhibition of SAM-dependent transmethylation drives epigenomic hypomethylation and overexpression of immune-stimulatory endogenous retroviral elements that engage cytosolic dsRNA sensors and induce IFN-β. We uncovered a previously unknown cellular signaling pathway that responds to extracellular DNA-derived metabolites, coupling nucleoside catabolism by adenosine deaminases to cellular IFN-β production.
Identifiers
What OpenQuestion holds
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.