ArticleDiabetologia2020
Extracellular HMGB1 exacerbates autoimmune progression and recurrence of type 1 diabetes by impairing regulatory T cell stability.
Article in Diabetologia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Antiglycation approach in selected autoimmune diseases: Where do we stand?Redox biology · 2026Review
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- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- Unlocking beta cell health: The clinical potential of extracellular vesicles in type 1 diabetes.Clinical and translational medicine · 2026Review
- Circulating levels of high mobility group box-1 and nucleophosmin/B23 proteins and clinical significance in debut non-small cell lung cancer patients.Scientific reports · 2026Article
- Association of serum HMGB1 and TLR4 levels with early-onset post-stroke depression in type 2 diabetes: a prospective cohort study.BMC neurology · 2026Article
- Investigating the protective effect of zinc supplementation on streptozotocin-induced pancreatic beta-cell damage via the HMGB1/TLR2/MAPK pathway.Iranian journal of basic medical sciences · 2026Article
- Taking its TOLL: the role of toll-like receptor 4 in human health and disease, and its potential as a therapeutic target.Frontiers in immunology · 2026Review
- Sex-specific differences of advanced glycation end products in diabetes.Nutrition & diabetes · 2025Review
- Electroacupuncture improves scopolamine hydrobromide induced dry eye in mice via inhibiting ocular surface inflammation and regulating the HMGB1-related signaling pathways.Frontiers in medicine · 2025Article
- High Mobility Group Box 1 (HMGB1): Molecular Signaling and Potential Therapeutic Strategies.Cells · 2024Review
- The Application Potential of the Regulation of Tregs Function by Irisin in the Prevention and Treatment of Immune-Related Diseases.Drug design, development and therapy · 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
- Article
- High Mobility Group Box 1: Biological Functions and Relevance in Oxidative Stress Related Chronic Diseases.Cells · 2022Review
- Knockout of high-mobility group box 1 in B16F10 melanoma cells induced host immunity-mediated suppression of in vivo tumor growth.Medical oncology (Northwood, London, England) · 2022Article
- Increased plasmablasts enhance T cell-mediated beta cell destruction and promote the development of type 1 diabetes.Molecular medicine (Cambridge, Mass.) · 2022Article
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 4 countries.
Funding
Abstract
aims/hypothesisHigh-mobility group box 1 (HMGB1), an evolutionarily conserved chromosomal protein, was rediscovered to be a 'danger signal' (alarmin) that alerts the immune system once released extracellularly. Therefore, it has been recognised contributing to the pathogenesis of autoimmune diabetes, but its exact impact on the initiation and progression of type 1 diabetes, as well as the related molecular mechanisms, are yet to be fully characterised.
methodsIn the current report, we employed NOD mice as a model to dissect the impact of blocking HMGB1 on the prevention, treatment and reversal of type 1 diabetes. To study the mechanism involved, we extensively examined the characteristics of regulatory T cells (Tregs) and their related signalling pathways upon HMGB1 stimulation. Furthermore, we investigated the relevance of our data to human autoimmune diabetes.
resultsNeutralising HMGB1 both delayed diabetes onset and, of particular relevance, reversed diabetes in 13 out of 20 new-onset diabetic NOD mice. Consistently, blockade of HMGB1 prevented islet isografts from autoimmune attack in diabetic NOD mice. Using transgenic reporter mice that carry a Foxp3 lineage reporter construct, we found that administration of HMGB1 impairs Treg stability and function. Mechanistic studies revealed that HMGB1 activates receptor for AGE (RAGE) and toll-like receptor (TLR)4 to enhance phosphatidylinositol 3-kinase (PI3K)-Akt-mechanistic target of rapamycin (mTOR) signalling, thereby impairing Treg stability and functionality. Indeed, high circulating levels of HMGB1 in human participants with type 1 diabetes contribute to Treg instability, suggesting that blockade of HMGB1 could be an effective therapy against type 1 diabetes in clinical settings. CONCLUSIONS/
interpretationThe present data support the possibility that HMGB1 could be a viable therapeutic target to prevent the initiation, progression and recurrence of autoimmunity in the setting of type 1 diabetes.
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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.