ArticleFree radical biology & medicine2012
Dysregulated TLR3-dependent signaling and innate immune activation in superoxide-deficient macrophages from nonobese diabetic mice.
Article in Free radical biology & medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Oxidative Stress, Post-Translational Modifications, and Type 1 Diabetes Pathogenesis.Immunological reviews · 2026Review
- Reactive Oxygen Species in Autoimmune Cells: Function, Differentiation, and Metabolism.Frontiers in immunology · 2021Review
- Role of Free Radical Formation in Murine Cytomegalovirus-Induced Hearing Loss.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2020Article
- The Role of Nucleic Acid Sensing in Controlling Microbial and Autoimmune Disorders.International review of cell and molecular biology · 2019Review
- Copper Regulates the Susceptibility of Zebrafish Larvae to Inflammatory Stimuli by Controlling Neutrophil/Macrophage Survival.Frontiers in immunology · 2019Article
- Redox-Sensitive Innate Immune Pathways During Macrophage Activation in Type 1 Diabetes.Antioxidants & redox signaling · 2018Review
- Redox-Dependent Inflammation in Islet Transplantation Rejection.Frontiers in endocrinology · 2018Review
- 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
- NADPH Oxidase-Derived Superoxide Provides a Third Signal for CD4 T Cell Effector Responses.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Regulation of B lymphocyte responses to Toll-like receptor ligand binding during diabetes prevention in non-obese diabetic (NOD) mice.Journal of diabetes · 2016Article
- Loss of NOX-Derived Superoxide Exacerbates Diabetogenic CD4 T-Cell Effector Responses in Type 1 Diabetes.Diabetes · 2015Article
- Article
- Loss of NADPH oxidase-derived superoxide skews macrophage phenotypes to delay type 1 diabetes.Diabetes · 2015Article
- Sumoylation modulates oxidative stress relevant to the viability and functionality of pancreatic beta cells.American journal of translational research · 2014Review
- The role of reactive oxygen species and proinflammatory cytokines in type 1 diabetes pathogenesis.Annals of the New York Academy of Sciences · 2013Review
- Radical innate regulation of autoimmune diabetes.Free radical biology & medicine · 2012Article
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7 authors at 1 institution in 1 country.
Funding
Abstract
In type 1 diabetes (T1D), reactive oxygen species (ROS) and proinflammatory cytokines produced by macrophages and other innate immune cells destroy pancreatic β cells while promoting autoreactive T cell maturation. Superoxide-deficient nonobese diabetic mice (NOD.Ncf1(m1J)) are resistant to spontaneous diabetes, revealing the integral role of ROS signaling in T1D. Here, we evaluate the innate immune activation state of bone marrow-derived macrophages (BM-Mϕ) from NOD and NOD.Ncf1(m1J) mice after poly(I:C)-induced Toll-like receptor 3 (TLR3) signaling. We show that ROS synthesis is required for efficient activation of the NF-κB signaling pathway and concomitant expression of TLR3 and the cognate adaptor molecule, TRIF. Poly(I:C)-stimulated NOD.Ncf1(m1J) BM-Mϕ exhibited a 2- and 10-fold decrease in TNF-α and IFN-β proinflammatory cytokine synthesis, respectively, in contrast to NOD BM-Mϕ. Optimal expression of IFN-α/β is not solely dependent on superoxide synthesis, but requires p47(phox) to function in a NOX-independent manner to mediate type I interferon synthesis. Interestingly, MHC-II I-A(g7) expression necessary for CD4 T cell activation is increased 2-fold relative to NOD, implicating a role for superoxide in I-A(g7) downregulation. These findings suggest that defective innate immune-pattern-recognition receptor activation and subsequent decrease in TNF-α and IFN-β proinflammatory cytokine synthesis necessary for autoreactive T cell maturation may contribute to the T1D protection observed in NOD.Ncf1(m1J) mice.
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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.