ArticleEMBO molecular medicine2010
DNA-dependent protein kinase catalytic subunit mediates T-cell loss in rheumatoid arthritis.
Article in EMBO molecular medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
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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
53 citing papers in PubMed, 67 citations in OpenAlex.
- Cytoplasmic relocation of nuclear Ku70 by Bruceine A augments cGAS-STING pathway-mediated anti-tumor immunity.Acta pharmaceutica Sinica. B · 2026Article
- Th17 cells require the DNA repair sensor xeroderma pigmentosum complementation Group C to control oxidative DNA damage in a murine model.Nature communications · 2026Article
- Investigating the relationship between osteoporosis and rheumatoid arthritis: prospective cohort study and genetic analyses.Therapeutic advances in musculoskeletal disease · 2026Article
- Immunosenescence in aging and neurodegenerative diseases: evidence, key hallmarks, and therapeutic implications.Translational neurodegeneration · 2025Review
- Unlocking the Therapeutic Potential of DNA-PKcs in Cancer: Comprehensive Insights into Mechanisms and Clinical Applications.Cancers · 2025Review
- Immune Aging in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Review
- An in-depth understanding of the role and mechanisms of T cells in immune organ aging and age-related diseases.Science China. Life sciences · 2025Review
- Senolytic treatment to rescue hallmarks of senescence in lymph node fibroblasts from patients with rheumatoid arthritis: Implications for premature aging and potential therapeutic intervention in early rheumatoid arthritis.Clinical and experimental immunology · 2025Article
- Subset-specific mitochondrial stress and DNA damage shape T cell responses to fever and inflammation.Science immunology · 2024Article
- The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.MedComm · 2024Review
- Immune aging - A mechanism in autoimmune disease.Seminars in immunology · 2023Review
- Mitochondria as disease-relevant organelles in rheumatoid arthritis.Clinical and experimental immunology · 2023Article
- Immunosenescence of T cells: a key player in rheumatoid arthritis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Review
- How Can We Improve the Vaccination Response in Older People? Part II: Targeting Immunosenescence of Adaptive Immunity Cells.International journal of molecular sciences · 2022Review
- T-Cell Aging-Associated Phenotypes in Autoimmune Disease.Frontiers in aging · 2022Review
- Hallmarks of the aging T-cell system.The FEBS journal · 2021Review
- DNA Damage Response in the Adaptive Arm of the Immune System: Implications for Autoimmunity.International journal of molecular sciences · 2021Review
- The immunology of rheumatoid arthritis.Nature immunology · 2021Review
- Molecular Mechanisms of Immunosenescene and Inflammaging: Relevance to the Immunopathogenesis and Treatment of Multiple Sclerosis.Frontiers in neurology · 2021Review
- The metabolic signature of T cells in rheumatoid arthritis.Current opinion in rheumatology · 2020Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
In the autoimmune syndrome rheumatoid arthritis (RA), T cells and T-cell precursors have age-inappropriate shortening of telomeres and accumulate deoxyribonucleic acid (DNA) double strand breaks. Whether damaged DNA elicits DNA repair activity and how this affects T-cell function and survival is unknown. Here, we report that naïve and resting T cells from RA patients are susceptible to undergo apoptosis. In such T cells, unrepaired DNA stimulates a p53-ataxia telangiectasia mutated-independent pathway involving the non-homologous-end-joining protein DNA-protein kinase catalytic subunit (DNA-PKcs). Upregulation of DNA-PKcs transcription, protein expression and phosphorylation in RA T cells co-occurs with diminished expression of the Ku70/80 heterodimer, limiting DNA repair capacity. Inhibition of DNA-PKcs kinase activity or gene silencing of DNA-PKcs protects RA T cells from apoptosis. DNA-PKcs induces T-cell death by activating the JNK pathway and upregulating the apoptogenic BH3-only proteins Bim and Bmf. In essence, in RA, the DNA-PKcs-JNK-Bim/Bmf axis transmits genotoxic stress into shortened survival of naïve resting T cells, imposing chronic proliferative turnover of the immune system and premature immunosenescence. Therapeutic blockade of the DNA-PK-dependent cell-death machinery may rejuvenate the immune system in RA.
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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.