ArticleFrontiers in immunology2022
Extracellular Nucleosomes Accelerate Microglial Inflammation
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Ferroptosis in depression: mechanisms, association, and therapeutic strategies.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Characterization of NLRP3 Inflammasome-Associated Hub Genes in the Progression of Diabetic Nephropathy.Immunity, inflammation and disease · 2026Article
- Acupuncture as a modulator of microglial polarization and pyroptosis in depression: evidence from a chronic unpredictable mild stress rat model.Metabolic brain disease · 2026Article
- C-type lectin-like domain family 2 (CLEC2D) promotes proliferation and migration of breast cancer and serves as a poor prognostic factor.Breast cancer (Tokyo, Japan) · 2026Article
- Review
- Neuroinflammation and stress-induced pathophysiology in major depressive disorder: mechanisms and therapeutic implications.Frontiers in cellular neuroscience · 2025Review
- Circulating Nucleosomes as a Novel Biomarker for Sepsis: A Scoping Review.Biomedicines · 2024Article
- Chronic Stress-Induced Neuroinflammation: Relevance of Rodent Models to Human Disease.International journal of molecular sciences · 2024Review
- Trained innate immunity as a potential link between preeclampsia and future cardiovascular disease.Frontiers in endocrinology · 2024Review
- C-type lectin receptor 2d forms homodimers and heterodimers with TLR2 to negatively regulate IRF5-mediated antifungal immunity.Nature communications · 2023Article
- Selective serotonin reuptake inhibitors regulate the interrelation between 5-HT and inflammation after myocardial infarction.BMC cardiovascular disorders · 2023Article
- Mitochondrial DNA induces nucleus pulposus cell pyroptosis via the TLR9-NF-κB-NLRP3 axis.Journal of translational medicine · 2023Article
- Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Damage-associated molecular patterns (DAMPs) are the primary promoter of progressive neuroinflammation and are associated with chronic stress-related emotional disorders. The present study investigated the role and mechanism of extracellular nucleosomes and histones, the newly defined DAMPs, in mice with chronic stress. C57BL/6 mice were exposed to chronic unpredictable mild stress (CUMS) and corticosterone drinking, respectively, for 4 weeks. Negative emotional behaviors were comprehensively investigated. Microglial morphology, oxidative stress, and inflammation, as well as C-type lectin receptor 2D (Clec2d) and Toll-like receptor 9 (TLR9) expression in medial prefrontal cortex (mPFC) were assessed with flow cytometer and cell sorting. Specifically, microglial pro-inflammatory activation and inflammation were further investigated with stereotactic injection of recombinant nucleosomes and histones in mPFC and further evaluated with AAV-Clec2d knocking-down, DNase I, and activated protein C (APC) pretreatment. Moreover, the rescue effect by AAV-Clec2d knocking-down was observed in mice with chronic stress. Mice with chronic stress were presented as obviously depressive- and anxiety-like behaviors and accompanied with significant microglial oxidative stress and inflammation, indicating by reactive oxygen species (ROS) production, primed nuclear factor-κB (NF-κB) signaling pathway, activated NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome, and upregulated Clec2d and TLR9 in mPFC, together with histones dictation in cerebrospinal fluid and extracellular trap formation. Stereotactic injection of nucleosomes was contributed to promote microglial inflammation rather than histones in mPFC, indicating that the pro-inflammatory role was derived from extracellular histones-bound DNA but not freely histones. AAV-Clec2d knocking-down, DNase I, and APC were all effective to inhibit nucleosome-induced microglial oxidative stress and inflammation. Moreover, AAV-Clec2d knocking-down in mice with chronic stress exhibited reduced microglial inflammation and improved negative emotional behaviors. Our findings reveal a novel mechanism of DAMP-associated inflammation that extracellular nucleosomes accelerate microglial inflammation
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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 Socratic graph.