ArticleThe Journal of clinical investigation2022
Purine nucleoside phosphorylase enables dual metabolic checkpoints that prevent T cell immunodeficiency and TLR7-associated autoimmunity.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- IMPDH inhibition enhances cytarabine efficacy in SAMHD1-expressing leukaemia cells via guanine nucleotide depletion.Molecular oncology · 2026Article
- Sjögren's disease metabolome reveals biomarker signatures to characterise patients and assess disease activity.RMD open · 2026Article
- Adipose tissue releases nucleosides.American journal of physiology. Cell physiology · 2026Article
- Purin Metabolism Is Crucial for Regulatory T Cell Stability and Function.European journal of immunology · 2025Review
- Guanine Crystal Formation at Physiological pH.Crystal growth & design · 2025Article
- The progress and prospects of targeting the adenosine pathway in cancer immunotherapy.Biomarker research · 2025Review
- SAMHD1 shapes deoxynucleotide triphosphate homeostasis by interconnecting the depletion and biosynthesis of different dNTPs.Nature communications · 2025Article
- D-ribose-5-phosphate inactivates YAP and functions as a metabolic checkpoint.Journal of hematology & oncology · 2025Article
- Candidate Genetic Loci Modifying the Colorectal Cancer Risk Caused by Lifestyle Risk Factors.Clinical and translational gastroenterology · 2025Article
- Landscape of targets within nucleoside metabolism for the modification of immune responses.Frontiers in oncology · 2025Review
- PNP as a Metabolic and Prognostic Driver of Breast Cancer Aggressiveness: Insights from Patient Tissue and Cell Models.Oncology research · 2025Article
- Ecological diversification of sea catfishes is accompanied by genome-wide signatures of positive selection.Nature communications · 2024Article
- Rediscovering the human thymus through cutting-edge technologies.The Journal of experimental medicine · 2024Review
- Understanding the interplay between dNTP metabolism and genome stability in cancer.Disease models & mechanisms · 2024Review
- Transcriptomic Analysis Reveals the Effect of Urea on Metabolism ofLife (Basel, Switzerland) · 2024Article
- Enzyme-activatable charge transfer in gold nanoclusters.Chemical science · 2024Article
- Targeting host deoxycytidine kinase mitigateseLife · 2024Article
- Spatially resolved metabolomics and isotope tracing reveal dynamic metabolic responses of dentate granule neurons with acute stimulation.Nature metabolism · 2023Article
- Spatially resolved metabolomics and isotope tracing reveal dynamic metabolic responses of dentate granule neurons with acute stimulation.Research square · 2023Article
- Inborn Errors of Purine Salvage and Catabolism.Metabolites · 2023Review
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Authors and funding
25 authors at 6 institutions in 4 countries.
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Abstract
Purine nucleoside phosphorylase (PNP) enables the breakdown and recycling of guanine nucleosides. PNP insufficiency in humans is paradoxically associated with both immunodeficiency and autoimmunity, but the mechanistic basis for these outcomes is incompletely understood. Here, we identify two immune lineage-dependent consequences of PNP inactivation dictated by distinct gene interactions. During T cell development, PNP inactivation is synthetically lethal with downregulation of the dNTP triphosphohydrolase SAMHD1. This interaction requires deoxycytidine kinase activity and is antagonized by microenvironmental deoxycytidine. In B lymphocytes and macrophages, PNP regulates Toll-like receptor 7 signaling by controlling the levels of its (deoxy)guanosine nucleoside ligands. Overriding this regulatory mechanism promotes germinal center formation in the absence of exogenous antigen and accelerates disease in a mouse model of autoimmunity. This work reveals that one purine metabolism gene protects against immunodeficiency and autoimmunity via independent mechanisms operating in distinct immune lineages and identifies PNP as a potentially novel metabolic immune checkpoint.
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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.