ArticleNature immunology2023
Pyrimidine de novo synthesis inhibition selectively blocks effector but not memory T cell development.
Article in Nature immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed.
- Integration of single-cell sequencing and transcriptomic analysis to identify novel diagnostic biomarkers for pre-eclampsia.BMC pregnancy and childbirth · 2026Article
- Granzyme A-expressing Terminal Effector T Cells Dedifferentiate into Long-lived Memory T Cells.Research square · 2026Article
- Metabolic tracing reveals IL-2 driven glutaminolysis and de novo pyrimidine synthesis in human natural killer cells.The Journal of biological chemistry · 2026Article
- Repurposing of Inhibitors of Plasmodial Aspartate Transcarbamoylase Toward Trypanosoma Cruzi.ChemMedChem · 2026Article
- A post-translational regulatory map of chronic antigen-driven human T cell dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Balancing Intrinsic and Extrinsic Factors in CD8Immune network · 2026Review
- Nucleotide Metabolic Reprogramming in Sepsis: From Immune-Cell Fate to Organ Injury and Precision Therapeutics.Journal of inflammation research · 2026Review
- Inhibition of pyrimidine de novo synthesis fosters Treg cells and reduces diabetes development in models of Type 1 Diabetes.Molecular metabolism · 2025Article
- Ensemble quantitation of absolute metabolite concentrations in T cells reveals conserved features of immunometabolism.bioRxiv : the preprint server for biology · 2025Article
- Inhibition of ENT1 relieves intracellular adenosine-mediated T cell suppression in cancer.Nature immunology · 2025Article
- DHODH modulates immune evasion of cancer cells via CDP-Choline dependent regulation of phospholipid metabolism and ferroptosis.Nature communications · 2025Article
- DHODH inhibition alters T cell metabolism limiting acute graft-versus-host disease while retaining graft-versus-leukemia response.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Landscape of targets within nucleoside metabolism for the modification of immune responses.Frontiers in oncology · 2025Review
- Asparagine availability controls germinal center B cell homeostasis.Science immunology · 2024Article
- Mitochondrial Dysfunction-Evoked DHODH Acetylation is Involved in Renal Cell Ferroptosis during Cisplatin-Induced Acute Kidney Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Extracellular domains of CARs reprogramme T cell metabolism without antigen stimulation.Nature metabolism · 2024Article
- DHODH inhibition represents a therapeutic strategy and improves abiraterone treatment in castration-resistant prostate cancer.Oncogene · 2024Article
- Inactivation of cytidine triphosphate synthase 1 prevents fatal auto-immunity in mice.Nature communications · 2024Article
- Pyrimidine nucleotide starvation induces a decrease in the number of effector T cells but not memory T cells.Cellular & molecular immunology · 2023Article
Corrections and comments
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Authors and funding
33 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Blocking pyrimidine de novo synthesis by inhibiting dihydroorotate dehydrogenase is used to treat autoimmunity and prevent expansion of rapidly dividing cell populations including activated T cells. Here we show memory T cell precursors are resistant to pyrimidine starvation. Although the treatment effectively blocked effector T cells, the number, function and transcriptional profile of memory T cells and their precursors were unaffected. This effect occurred in a narrow time window in the early T cell expansion phase when developing effector, but not memory precursor, T cells are vulnerable to pyrimidine starvation. This vulnerability stems from a higher proliferative rate of early effector T cells as well as lower pyrimidine synthesis capacity when compared with memory precursors. This differential sensitivity is a drug-targetable checkpoint that efficiently diminishes effector T cells without affecting the memory compartment. This cell fate checkpoint might therefore lead to new methods to safely manipulate effector T cell responses.
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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.