ArticleDiabetes2015
Loss of NADPH oxidase-derived superoxide skews macrophage phenotypes to delay 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 62 papers.
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Who cites it
62 citing papers in PubMed, 104 citations in OpenAlex.
- Oxidative Stress, Post-Translational Modifications, and Type 1 Diabetes Pathogenesis.Immunological reviews · 2026Review
- Dissolvable antimicrobial microneedles loaded with bone marrow mesenchymal stem cell-derived migrasomes for diabetes wound treatment.Journal of nanobiotechnology · 2026Article
- Amino acid metabolism modulates macrophage polarization: implications for autoimmune-related diseases.Frontiers in immunology · 2026Review
- From Defense to Disease: NADPH Oxidase in Cellular Function and Dysregulation.Journal of immunology research · 2026Review
- Dual ROS/pH-responsive mangiferin-loaded smart microneedles for precision therapy of wound infections.Materials today. Bio · 2025Article
- Environmental Mechanisms Influencing the Pathogenesis and Progression of Type 1 Diabetes.International journal of molecular sciences · 2025Review
- The M2 Macrophages Importance Role in Psoriasis.Immunity, inflammation and disease · 2025Review
- New mesenchymal stem/stromal cell-based strategies for osteoarthritis treatment: targeting macrophage-mediated inflammation to restore joint homeostasis.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Could hypoxic conditioning augment the potential of mesenchymal stromal cell-derived extracellular vesicles as a treatment for type 1 diabetes?Stem cell research & therapy · 2025Review
- Reactive Oxygen Species in Asthma: Regulators of Macrophage Polarization and Therapeutic Implications: A Narrative Review.Journal of asthma and allergy · 2025Review
- Electroactive electrospun nanoplatform combined with electrical stimulation modulates anti-inflammatory macrophage polarization for enhanced wound healing.Frontiers in bioengineering and biotechnology · 2025Article
- Interactions between islet-resident macrophages and β cells in diabetes.Frontiers in immunology · 2025Review
- Cell-Type-Specific ROS-AKT/mTOR-Autophagy Interplay-Should It Be Addressed in Periimplantitis?Diagnostics (Basel, Switzerland) · 2024Review
- Role of ROS and autophagy in the pathological process of atherosclerosis.Journal of physiology and biochemistry · 2024Review
- Importance of Studying Non-Coding RNA in Children and Adolescents with Type 1 Diabetes.Biomedicines · 2024Review
- Nutrient availability regulates the secretion and function of immune cell-derived extracellular vesicles through metabolic rewiring.Science advances · 2024Article
- HTRA2/OMI-Mediated Mitochondrial Quality Control Alters Macrophage Polarization Affecting Systemic Chronic Inflammation.International journal of molecular sciences · 2024Review
- Review
- Modulation of Innate Immune Memory Dynamics by Subcellular Reactive Oxygen Species.Antioxidants & redox signaling · 2023Review
- Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Macrophages are early islet-infiltrating cells seen in type 1 diabetes (T1D). While proinflammatory M1 macrophages induce T1D, M2 macrophages have been shown to delay this autoimmune disease in nonobese diabetic (NOD) mice, but the environmental cues that govern macrophage polarization and differentiation remain unresolved. We previously demonstrated the importance of reactive oxygen species (ROS) in T1D, as NOD mice deficient in NADPH oxidase (NOX)-derived superoxide (Ncf1(m1J)) were protected against T1D partly because of blunted Toll-like receptor-dependent macrophage responses. We provide evidence that NOX-derived ROS contribute to macrophage differentiation in T1D. During spontaneous diabetes progression, T1D-resistant NOD.Ncf1(m1J) islet-resident macrophages displayed a dampened M1 and increased M2 phenotype. The transfer of diabetogenic T cells into NOX-deficient NOD.Rag.Ncf1(m1J) recipients resulted in decreased TNF-α(+) and IL-1β(+) islet-infiltrating M1 macrophages and a concomitant enhancement in arginase-1(+) M2 macrophages. Mechanistic analysis of superoxide-deficient bone marrow-derived macrophages revealed a marked diminution in a proinflammatory M1 phenotype due to decreased P-STAT1 (Y701) and interferon regulatory factor 5 compared with NOD mice. We have therefore defined a novel mechanistic link between NOX-derived ROS and macrophage phenotypes, and implicated superoxide as an important factor in macrophage differentiation. Thus, targeting macrophage redox status may represent a promising therapy in halting human T1D.
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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.