ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
The Deubiquitinase OTUD1 Suppresses Secretory Neutrophil Polarization And Ameliorates Immunopathology of Periodontitis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. 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, 28 citations in OpenAlex.
- Ovarian tumor domain-containing protein 1 deficiency attenuates metabolic dysfunction-associated steatotic liver disease by promoting the ubiquitination of HSP90α in hepatocytes.Molecular biomedicine · 2026Article
- Magnetoelectric nanoparticles drive TAF9BScience advances · 2026Article
- OTU deubiquitinases in disease: roles and targeting.Trends in molecular medicine · 2026Review
- Therapeutic Potential of the Deubiquitinase BRCC3 in Attenuating Ischemic Myocardial Injury and Ventricular Remodeling.Research (Washington, D.C.) · 2026Article
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- OTUD1 positively regulates microglia neuroinflammation and promotes the pathogenesis of Alzheimer's disease by deubiquitinating C/EBPβ.Acta pharmacologica Sinica · 2025Article
- CD81eLife · 2025Article
- The research progress on periodontitis by the National Natural Science Foundation of China.International journal of oral science · 2025Review
- Single-cell atlas of human gingiva unveils a NETs-related neutrophil subpopulation regulating periodontal immunity.Journal of advanced research · 2025Article
- Ubiquitin-Proteasome System in Periodontitis: Mechanisms and Clinical Implications.Cell proliferation · 2025Review
- OTUD1 inhibits osteoclast differentiation and osteoclastic bone loss through deubiquitinating and stabilizing PRDX1.Theranostics · 2025Article
- Association between neutrophil-percentage-to-albumin ratio and periodontitis: insights from a population-based study.Frontiers in nutrition · 2025Article
- Association between the Dietary Index for Gut Microbiota and periodontitis: mediation by systemic inflammation.Frontiers in nutrition · 2025Article
- Anti-inflammatory effects of natural polysaccharides: molecular mechanisms and nanotherapeutic applications.Frontiers in immunology · 2025Review
- The deubiquitinase OTUD1 stabilizes NRF2 to alleviate hepatic ischemia/reperfusion injury.Redox biology · 2024Article
- Salicin alleviates periodontitis via Tas2r143/gustducin signaling in fibroblasts.Frontiers in immunology · 2024Article
- The Deubiquitinase OTUD1 Suppresses Secretory Neutrophil Polarization And Ameliorates Immunopathology of Periodontitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
Abstract
Tissue-infiltrating neutrophils (TINs) secrete various signaling molecules to establish paracrine communication within the inflammatory milieu. It is imperative to identify molecular mediators that control this secretory phenotype of TINs. The present study uncovers a secretory neutrophil subset that exhibits increased pro-inflammatory cytokine production and enhanced migratory capacity which is highly related with periodontal pathogenesis. Further analysis identifies the OTU domain-containing protein 1 (OTUD1) plays a regulatory role in this secretory neutrophil polarization. In human and mouse periodontitis, the waning of inflammation is correlated with OTUD1 upregulation, whereas severe periodontitis is induced when neutrophil-intrinsic OTUD1 is depleted. Mechanistically, OTUD1 interacts with SEC23B, a component of the coat protein II complex (COPII). By removing the K63-linked polyubiquitin chains on SEC23B Lysine 81, the deubiquitinase OTUD1 negatively regulates the COPII secretory machinery and limits protein ER-to-Golgi trafficking, thus restricting the surface expression of integrin-regulated proteins, CD9 and CD47. Accordingly, blockade of protein transport by Brefeldin A (BFA) curbs recruitment of Otud1-deficient TINs and attenuates inflammation-induced alveolar bone destruction. The results thus identify OTUD1 signaling as a negative feedback loop that limits the polarization of neutrophils with secretory phenotype and highlight the potential application of BFA in the treatment of periodontal inflammation.
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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 Socratic graph.