ArticleJournal of immunology (Baltimore, Md. : 1950)2012
A deficiency in nucleoside salvage impairs murine lymphocyte development, homeostasis, and survival.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- A pilot clinical trial of oral tetrahydrouridine/decitabine for noncytotoxic epigenetic therapy of chemoresistant lymphoid malignancies.Seminars in hematology · 2021Trial
- Deoxycytidine kinase inhibition: Rewiring tumor nucleotide metabolism for therapeutic gain.Nucleosides, nucleotides & nucleic acids · 2026Review
- Review
- DCK is a promising prognostic biomarker and correlated with immune infiltrates in hepatocellular carcinoma.World journal of surgical oncology · 2020Article
- Fine-Tuning of CD8(+) T Cell Mitochondrial Metabolism by the Respiratory Chain Repressor MCJ Dictates Protection to Influenza Virus.Immunity · 2016Article
- Regulation of nucleotide metabolism by mutant p53 contributes to its gain-of-function activities.Nature communications · 2015Article
- Structure-guided development of deoxycytidine kinase inhibitors with nanomolar affinity and improved metabolic stability.Journal of medicinal chemistry · 2014Article
- Zidovudine induces downregulation of mitochondrial deoxynucleoside kinases: implications for mitochondrial toxicity of antiviral nucleoside analogs.Antimicrobial agents and chemotherapy · 2014Article
- Mitochondria are gate-keepers of T cell function by producing the ATP that drives purinergic signaling.The Journal of biological chemistry · 2014Article
- Long-term in vivo monitoring of mouse and human hematopoietic stem cell engraftment with a human positron emission tomography reporter gene.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Deoxycytidine kinase promotes the migration and invasion of fibroblast-like synoviocytes from rheumatoid arthritis patients.International journal of clinical and experimental pathology · 2013Article
- Nucleoside salvage pathway kinases regulate hematopoiesis by linking nucleotide metabolism with replication stress.The Journal of experimental medicine · 2012Article
- Dissecting immunity by germline mutagenesis.Immunology · 2012Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The homeostasis of the immune system is tightly controlled by both cell-extrinsic and -intrinsic mechanisms. These regulators, not all known to date, drive cells in and out of quiescence when and where required to allow the immune system to function. In this article, we describe a deficiency in deoxycytidine kinase (DCK), one of the major enzymes of the nucleoside salvage pathway, which affects peripheral T cell homeostatic proliferation and survival. As a result of an N-ethyl-N-nitrosourea-induced mutation in the last α helix of DCK, a functionally null protein has been generated in the mouse and affects the composition of the hematopoietic system. Both B and T lymphocyte development is impaired, leading to a state of chronic lymphopenia and to a significant increase in the number of myeloid cells and erythrocytes. In the periphery, we found that mutant lymphocytes adopt a CD44(high)CD62L(low) memory phenotype, with high levels of proliferation and apoptosis. These phenotypes are notably the result of a cell-extrinsic-driven lymphopenia-induced proliferation as wild-type cells transferred into DCK-deficient recipients adopt the same profile. In addition, DCK also regulates lymphocyte quiescence in a cell-intrinsic manner. These data establish dCK as a new regulator of hematopoietic integrity and lymphocyte quiescence and survival.
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Registered trials
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