ArticleThe Journal of clinical investigation2016
NADPH oxidase deficiency underlies dysfunction of aged CD8+ Tregs.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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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
78 citing papers in PubMed.
- Role of regulatory T cells in acute myeloid leukemia patients undergoing relapse-preventive immunotherapy.Cancer immunology, immunotherapy : CII · 2017Trial
- The Role of MicroRNAs in Treg-Derived Extracellular Vesicles: A Narrative Review Focusing on Immune-Related Diseases.Journal of immunology research · 2026Review
- Cancer stem cell programs S-nitrosylation and deubiquitination of FoxP3 protein to promote regulatory T cell differentiation.Frontiers in immunology · 2026Article
- Interferon-stimulated Viperin impairs Treg function in autoimmune thrombocytopenia.Cell communication and signaling : CCS · 2025Article
- Cytotoxic T Cells: Kill, Memorize, and Mask to Maintain Immune Homeostasis.International journal of molecular sciences · 2025Review
- Oxidative stress in cancer: from tumor and microenvironment remodeling to therapeutic frontiers.Molecular cancer · 2025Review
- Immune Aging in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Review
- Article
- The Role of NADPH Oxidase 2 in Leukocytes.Antioxidants (Basel, Switzerland) · 2025Review
- NDUFS4, a mitochondrial complex I subunit, is essential for T-cell metabolic fitness and immune function.Frontiers in immunology · 2025Article
- Impact of NF-κB and reactive oxygen species on intracellular BAFF/APRIL expression in ANCA-associated vasculitis: focusing on the effect of resveratrol.Frontiers in immunology · 2025Article
- Nitric oxide facilitates the S-nitrosylation and deubiquitination of Notch1 protein to maintain cancer stem cells in human NSCLC.Journal of cellular and molecular medicine · 2024Article
- NADPH oxidase in B cells and macrophages protects against murine lupus by regulation of TLR7.JCI insight · 2024Article
- Immune checkpoints in autoimmune vasculitis.Best practice & research. Clinical rheumatology · 2024Review
- Review
- Giant Cell Arteritis: Advances in Understanding Pathogenesis and Implications for Clinical Practice.Cells · 2024Review
- Oxidative stress in pituitary neuroendocrine tumors: Affecting the tumor microenvironment and becoming a new target for pituitary neuroendocrine tumor therapy.CNS neuroscience & therapeutics · 2023Review
- Immune aging - A mechanism in autoimmune disease.Seminars in immunology · 2023Review
- CD8Journal of clinical medicine · 2023Article
- Immunology of Giant Cell Arteritis.Circulation research · 2023Review
18 more citing papers are in PubMed but not listed here.
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9 authors.
Funding
Abstract
Immune aging results in progressive loss of both protective immunity and T cell-mediated suppression, thereby conferring susceptibility to a combination of immunodeficiency and chronic inflammatory disease. Here, we determined that older individuals fail to generate immunosuppressive CD8+CCR7+ Tregs, a defect that is even more pronounced in the age-related vasculitic syndrome giant cell arteritis. In young, healthy individuals, CD8+CCR7+ Tregs are localized in T cell zones of secondary lymphoid organs, suppress activation and expansion of CD4 T cells by inhibiting the phosphorylation of membrane-proximal signaling molecules, and effectively inhibit proliferative expansion of CD4 T cells in vitro and in vivo. We identified deficiency of NADPH oxidase 2 (NOX2) as the molecular underpinning of CD8 Treg failure in the older individuals and in patients with giant cell arteritis. CD8 Tregs suppress by releasing exosomes that carry preassembled NOX2 membrane clusters and are taken up by CD4 T cells. Overexpression of NOX2 in aged CD8 Tregs promptly restored suppressive function. Together, our data support NOX2 as a critical component of the suppressive machinery of CD8 Tregs and suggest that repairing NOX2 deficiency in these cells may protect older individuals from tissue-destructive inflammatory disease, such as large-vessel vasculitis.
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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.