ArticleDiabetes2015
Loss of NOX-Derived Superoxide Exacerbates Diabetogenic CD4 T-Cell Effector Responses in Type 1 Diabetes.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Oxidative Stress, Post-Translational Modifications, and Type 1 Diabetes Pathogenesis.Immunological reviews · 2026Review
- Metabolic Blockade of Glycolysis Diminishes Autoreactive CD4 T-Cell Effector Responses in Type 1 Diabetes.Diabetes · 2026Article
- The type 1 and type 3 immune responses underlying the tissue inflammation associated with NOX2 deficiency.Frontiers in immunology · 2026Review
- Panoramic description of ROS-based nanotechnology for osteomyelitis therapy: Challenges, opportunities, and prospects.Theranostics · 2026Review
- Environmental Mechanisms Influencing the Pathogenesis and Progression of Type 1 Diabetes.International journal of molecular sciences · 2025Review
- The Role of NADPH Oxidase 2 in Leukocytes.Antioxidants (Basel, Switzerland) · 2025Review
- MDA5-dependent responses contribute to autoimmune diabetes progression and hindrance.JCI insight · 2023Article
- Engineered Extracellular Vesicles in Treatment of Type 1 Diabetes Mellitus: A Prospective Review.Biomedicines · 2022Review
- Activation pathways that drive CD4Immunological reviews · 2022Review
- Metabolic Reprogramming and Reactive Oxygen Species in T Cell Immunity.Frontiers in immunology · 2021Review
- Reactive Oxygen Species in Autoimmune Cells: Function, Differentiation, and Metabolism.Frontiers in immunology · 2021Review
- The Role of β Cell Stress and Neo-Epitopes in the Immunopathology of Type 1 Diabetes.Frontiers in endocrinology · 2020Review
- Superoxide Production by NADPH Oxidase Intensifies Macrophage Antiviral Responses during Diabetogenic Coxsackievirus Infection.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Islet encapsulation with polyphenol coatings decreases pro-inflammatory chemokine synthesis and T cell trafficking.Biomaterials · 2017Article
- NOX2 deficiency alters macrophage phenotype through an IL-10/STAT3 dependent mechanism: implications for traumatic brain injury.Journal of neuroinflammation · 2017Article
- T Cell-Mediated Beta Cell Destruction: Autoimmunity and Alloimmunity in the Context of Type 1 Diabetes.Frontiers in endocrinology · 2017Review
- Immunometabolism and autoimmunity.Immunology and cell biology · 2016Review
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 6 institutions in 1 country.
Funding
Abstract
Reactive oxygen species (ROS) play prominent roles in numerous biological systems. While classically expressed by neutrophils and macrophages, CD4 T cells also express NADPH oxidase (NOX), the superoxide-generating multisubunit enzyme. Our laboratory recently demonstrated that superoxide-deficient nonobese diabetic (NOD.Ncf1(m1J)) mice exhibited a delay in type 1 diabetes (T1D) partially due to blunted IFN-γ synthesis by CD4 T cells. For further investigation of the roles of superoxide on CD4 T-cell diabetogenicity, the NOD.BDC-2.5.Ncf1(m1J) (BDC-2.5.Ncf1(m1J)) mouse strain was generated, possessing autoreactive CD4 T cells deficient in NOX-derived superoxide. Unlike NOD.Ncf1(m1J), stimulated BDC-2.5.Ncf1(m1J) CD4 T cells and splenocytes displayed elevated synthesis of Th1 cytokines and chemokines. Superoxide-deficient BDC-2.5 mice developed spontaneous T1D, and CD4 T cells were more diabetogenic upon adoptive transfer into NOD.Rag recipients due to a skewing toward impaired Treg suppression. Exogenous superoxide blunted exacerbated Th1 cytokines and proinflammatory chemokines to approximately wild-type levels, concomitant with reduced IL-12Rβ2 signaling and P-STAT4 (Y693) activation. These results highlight the importance of NOX-derived superoxide in curbing autoreactivity due, in part, to control of Treg function and as a redox-dependent checkpoint of effector T-cell responses. Ultimately, our studies reveal the complexities of free radicals in CD4 T-cell responses.
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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.