ArticleJournal of immunology (Baltimore, Md. : 1950)2008
Restoration of adenosine deaminase-deficient human thymocyte development in vitro by inhibition of deoxynucleoside kinases.
Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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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.
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- Preventing ATP Degradation by ASO-Mediated Knockdown of CD39 and CD73 Results in A2aR-Independent Rescue of T Cell Proliferation.Molecular therapy. Nucleic acids · 2020Article
- Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency.The Journal of allergy and clinical immunology · 2019Review
- Pathophysiological Role of Purines and Pyrimidines in Neurodevelopment: Unveiling New Pharmacological Approaches to Congenital Brain Diseases.Frontiers in pharmacology · 2017Review
- Adenosine Deaminase Deficiency - More Than Just an Immunodeficiency.Frontiers in immunology · 2016Review
- Structural characterization of new deoxycytidine kinase inhibitors rationalizes the affinity-determining moieties of the molecules.Acta crystallographica. Section D, Biological crystallography · 2014Article
- Hypoxia-induced deoxycytidine kinase expression contributes to apoptosis in chronic lung disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- Regulation of lymphocyte function by adenosine.Arteriosclerosis, thrombosis, and vascular biology · 2012Review
- Requirement for deoxycytidine kinase in T and B lymphocyte development.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in the gene encoding adenosine deaminase (ADA), a purine salvage enzyme, lead to immunodeficiency in humans. Although ADA deficiency has been analyzed in cell culture and murine models, information is lacking concerning its impact on the development of human thymocytes. We have used chimeric human/mouse fetal thymic organ culture to study ADA-deficient human thymocyte development in an "in vivo-like" environment where toxic metabolites accumulate in situ. Inhibition of ADA during human thymocyte development resulted in a severe reduction in cellular expansion as well as impaired differentiation, largely affecting mature thymocyte populations. Thymocyte differentiation was not blocked at a discrete stage; rather, the paucity of mature thymocytes was due to the induction of apoptosis as evidenced by activation of caspases and was accompanied by the accumulation of intracellular dATP. Inhibition of adenosine kinase and deoxycytidine kinase prevented the accumulation of dATP and restored thymocyte differentiation and proliferation. Our work reveals that multiple deoxynucleoside kinases are involved in the phosphorylation of deoxyadenosine when ADA is absent, and suggests an alternate therapeutic strategy for treatment of ADA-deficient patients.
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Registered trials
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