ArticleDiabetes2008
Extracellular high-mobility group box 1 acts as an innate immune mediator to enhance autoimmune progression and diabetes onset in NOD mice.
Article in Diabetes, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 105 citations in OpenAlex.
- Immunomodulatory effects and improved outcomes with cisplatin- versus carboplatin-based chemotherapy plus atezolizumab in urothelial cancer.Cell reports. Medicine · 2024Trial
- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- PANoptosis in diabetes: immunometabolic insights and treatments.Apoptosis : an international journal on programmed cell death · 2026Review
- High Mobility Group Box 1 (HMGB1): Molecular Signaling and Potential Therapeutic Strategies.Cells · 2024Review
- HMGB1 and Toll-like receptors: potential therapeutic targets in autoimmune diseases.Molecular medicine (Cambridge, Mass.) · 2023Review
- The relationship between HMGB1 and autophagy in the pathogenesis of diabetes and its complications.Frontiers in endocrinology · 2023Review
- Review
- Article
- Damage-associated Molecular Patterns in Clinical and Animal Models of Uveitis.Ocular immunology and inflammation · 2022Article
- Expatiating the molecular approaches of HMGB1 in diabetes mellitus: Highlighting signalling pathways via RAGE and TLRs.Molecular biology reports · 2021Review
- Role of DNA-LL37 complexes in the activation of plasmacytoid dendritic cells and monocytes in subjects with type 1 diabetes.Scientific reports · 2020Article
- Leuconostoc mesenteroides fermentation produces butyric acid and mediates Ffar2 to regulate blood glucose and insulin in type 1 diabetic mice.Scientific reports · 2020Article
- Extracellular HMGB1 exacerbates autoimmune progression and recurrence of type 1 diabetes by impairing regulatory T cell stability.Diabetologia · 2020Article
- Loss of ubiquitin-conjugating enzyme E2 (Ubc9) in macrophages exacerbates multiple low-dose streptozotocin-induced diabetes by attenuating M2 macrophage polarization.Cell death & disease · 2019Article
- BDNF Alleviates Neuroinflammation in the Hippocampus of Type 1 Diabetic Mice via Blocking the Aberrant HMGB1/RAGE/NF-κB Pathway.Aging and disease · 2019Article
- Serum levels of the high-mobility group box 1 protein (HMGB1) in children with type 1 diabetes mellitus: case-control study.Central-European journal of immunology · 2019Article
- The Modulation of Regulatory T Cells via HMGB1/PTEN/β-Catenin Axis in LPS Induced Acute Lung Injury.Frontiers in immunology · 2019Article
- Loss of Jak2 protects cardiac allografts from chronic rejection by attenuating Th1 response along with increased regulatory T cells.American journal of translational research · 2019Article
- Both conditional ablation and overexpression of E2 SUMO-conjugating enzyme (UBC9) in mouse pancreatic beta cells result in impaired beta cell function.Diabetologia · 2018Article
- Cellular death, reactive oxygen species (ROS) and diabetic complications.Cell death & disease · 2018Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe implication of innate immunity in type 1 diabetes development has long been proposed. High-mobility group box 1 (HMGB1), an evolutionarily conserved chromosomal protein, was recently recognized to be a potent innate inflammatory mediator when released extracellularly. We sought to test the hypothesis that HMGB1 acts as an innate immune mediator implicated in type 1 diabetes pathogenesis. RESEARCH DESIGN AND
methodsEight- and 12-week-old NOD mice were treated with an HMGB1 neutralizing antibody once a week until 25 weeks of age and monitored for insulitis progression and diabetes onset. The underlying mechanisms of HMGB1 regulation of autoimmune response were further explored.
resultsDuring autoimmunity, HMGB1 can be passively released from damaged pancreatic beta-cells and actively secreted by islet infiltrated immune cells. Extracellular HMGB1 is potent in inducing NOD dendritic cell maturation and stimulating macrophage activation. Blockade of HMGB1 significantly inhibited insulitis progression and diabetes development in both 8- and 12-week-old NOD mice. HMGB1 antibody treatment decreased the number and maturation of pancreatic lymph node (PLN) CD11c(++)CD11b(+) dendritic cells, a subset of dendritic cells probably associated with autoantigen presentation to naïve T-cells, but increased the number for PLN CD4(+)Foxp3(+) regulatory T-cells. Blockade of HMGB1 also decreased splenic dendritic cell allo-stimulatory capability associated with increased tolergenic CD11c(+)CD8a(+) dendritic cells. Interestingly, the number of CD8(+)interferon-gamma(+) (Tc1) T-cells was increased in the PLNs and spleen after blockade of HMGB1, which could be associated with retarded migration of activated autoreactive T-cells into the pancreatic islets.
conclusionsExtracellular HMGB1 functions as a potent innate immune mediator contributing to insulitis progression and diabetes onset.
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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.