ArticleScience signaling2010
The nonphagocytic NADPH oxidase Duox1 mediates a positive feedback loop during T cell receptor signaling.
Article in Science signaling, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 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
74 citing papers in PubMed, 137 citations in OpenAlex.
- Boosting T cell antioxidant capacity: A strategic approach to overcome immunosuppression in solid tumors.Redox biology · 2026Review
- The distinct roles of ROS in tumor immunity: from mechanisms to immunotherapeutic applications.Journal of hematology & oncology · 2026Review
- Selective disruption of lipid peroxide homeostasis in intratumoral regulatory T cells by targeting FSP1 enhances cancer immunity.Science advances · 2026Article
- Germline determinants of toxicity and efficacy in patients with large B-cell lymphoma treated with CAR T-cell therapy.Journal for immunotherapy of cancer · 2025Article
- Iron overload in HFE-related hemochromatosis severely impairs Vδ2+ γδ T-cell homeostasis.Blood · 2025Article
- The Role of NADPH Oxidase 2 in Leukocytes.Antioxidants (Basel, Switzerland) · 2025Review
- Tumor microenvironment regulation by reactive oxygen species-mediated inflammasome activation.Archives of pharmacal research · 2025Review
- Iron and energy metabolic interactions in Treg-mediated immune regulation.Frontiers in immunology · 2025Review
- The role of autophagy in cancer: from molecular mechanism to therapeutic window.Frontiers in immunology · 2025Review
- Fluorescence imaging sheds light on the immune evasion mechanisms of hepatic stellate cells mediated by superoxide anion.Communications biology · 2024Article
- Review
- The relationship of redox signaling with the risk for atherosclerosis.Frontiers in pharmacology · 2024Review
- Treatment with Exogenously Added Catalase Alters CD8 T Cell Memory Differentiation and Function.Advanced biology · 2023Article
- Diet-induced obesity worsens allergen-induced type 2/type 17 inflammation in airways by enhancing DUOX1 activation.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- NAADP-Evoked CaHandbook of experimental pharmacology · 2023Article
- Reactive oxygen species formation and its effect on CD4Frontiers in immunology · 2023Review
- Rapid increase in transferrin receptor recycling promotes adhesion during T cell activation.BMC biology · 2022Article
- Macrophage-intrinsic DUOX1 contributes to type 2 inflammation and mucus metaplasia during allergic airway disease.Mucosal immunology · 2022Article
- The role of ROS in tumour development and progression.Nature reviews. Cancer · 2022Review
- Supplying the trip to antibody production-nutrients, signaling, and the programming of cellular metabolism in the mature B lineage.Cellular & molecular immunology · 2022Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Production of reactive oxygen species, often by NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidases, plays a role in the signaling responses of cells to many receptor stimuli. Here, we describe the function of the calcium-dependent, nonphagocytic NADPH oxidase Duox1 in primary human CD4(+) T cells and cultured T cell lines. Duox1 bound to inositol 1,4,5-trisphosphate receptor 1 and was required for early T cell receptor (TCR)-stimulated production of hydrogen peroxide (H(2)O(2)) through a pathway that was dependent on TCR-proximal kinases. Transient or stable knockdown of Duox1 inhibited TCR signaling, especially phosphorylation of tyrosine-319 of zeta chain-associated protein kinase of 70 kilodaltons (ZAP-70), store-operated entry of calcium ions (Ca(2+)), and activation of extracellular signal-regulated kinase. The production of cytokines was also inhibited by knockdown of Duox1. Duox1-mediated inactivation of Src homology 2 domain-containing protein tyrosine phosphatase 2 promoted the phosphorylation of ZAP-70 and its association with the Src family tyrosine kinase Lck and the CD3zeta chain of the TCR complex. Thus, we suggest that activation of Duox1, downstream of proximal TCR signals, generates H(2)O(2) that acts in a positive feedback loop to enhance and sustain further TCR signaling.
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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.