ArticleCell death & disease2021
Extracellular vesicles package dsDNA to aggravate Crohn's disease by activating the STING pathway.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT05916274 (Pro-inflammatory Role of Extracellular DNA in Inflammatory Bowel Disease in Children), which is not on this map. Cited by 49 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Pro-inflammatory Role of Extracellular DNA in Inflammatory Bowel Disease in Children: Study of the cGAS-STING Pathway
Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
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- Spatial architecture of immunometabolism: Mitochondrial‑organelle interfaces in immune signaling (Review).International journal of molecular medicine · 2026Review
- Context-dependent actions of STING pathway in colitis and associated colon cancer.Genes & diseases · 2026Review
- Machine learning-driven prioritization and experimental validation of traditional Chinese medicine-derived STING-inhibitory candidates.Molecular diversity · 2026Article
- Nanotechnology-driven STING regulation for on-demand therapy.Acta pharmaceutica Sinica. B · 2026Review
- Dysfunction of mitochondria in intestinal epithelial cells: a key player in the pathogenesis of inflammatory bowel diseases.Gastroenterology report · 2026Review
- Danthron Attenuates Intestinal Inflammation by Modulating Oxidative Stress via the EGFR-PI3K-AKT and Nrf2-HO-1 Pathways.Antioxidants (Basel, Switzerland) · 2026Article
- Myeloperoxidase-DNA complex: a marker and combined target for Pseudomonas aeruginosa-associated bronchiectasis.AMB Express · 2026Article
- Acupoint Catgut Embedding Ameliorates Ulcerative Colitis in Association with Modulation of cGAS-STING Signaling and M1-Like/M2-Like Macrophage Markers.Journal of inflammation research · 2026Article
- STING pathway contributes to Steroid-Hyporesponsive Lung Inflammation in DSS-induced colitis mice model.PloS one · 2026Article
- Extracellular vesicle-mediated immune-metabolic crosstalk: research advances in inflammatory regulation and the pathogenesis of metabolic diseases.Frontiers in immunology · 2026Review
- cGAS-STING signaling pathway as a therapeutic target in human diseases.Chinese medical journal · 2025Review
- The Immunogenic Role of Self-DNA in T Cell Immunity.Clinical reviews in allergy & immunology · 2025Review
- Colorectal Cancer Cells-Derived Exosomal PIK3CA Mutation DNA Promotes Tumor Metastasis by Activating Fibroblast and Affecting Tumor Metastatic Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Exosomes in inflammation and cancer: from bench to bedside applications.Molecular biomedicine · 2025Review
- Macrophages Internalize Epithelial-Derived Extracellular Vesicles That Contain Ferritin via the Macrophage Scavenger Receptor 1 to Promote Inflammatory Bowel Disease.Journal of extracellular vesicles · 2025Article
- Inflammatory Bowel Disease (IBD)-Associated Colorectal Cancer (CRC): Is cGAS-STING Pathway Targeting the Key to Chemoprevention?International journal of molecular sciences · 2025Review
- Birch pollen allergen-induced dsDNA release activates cGAS-STING signaling and type 2 immune response in mice.iScience · 2025Article
- Microscopic messengers: Extracellular vesicles shaping gastrointestinal health and disease.Physiological reports · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Crohn's disease (CD) is an intestinal immune-dysfunctional disease. Extracellular vesicles (EVs) are membrane-enclosed particles full of functional molecules, e.g., nuclear acids. Recently, EVs have been shown to participate in the development of CD by realizing intercellular communication among intestinal cells. However, the role of EVs carrying double-strand DNA (dsDNA) shed from sites of intestinal inflammation in CD has not been investigated. Here we isolated EVs from the plasma or colon lavage of murine colitis and CD patients. The level of exosomal dsDNA, including mtDNA and nDNA, significantly increased in murine colitis and active human CD, and was positively correlated with the disease activity. Moreover, the activation of the STING pathway was verified in CD. EVs from the plasma of active human CD triggered STING activation in macrophages in vitro. EVs from LPS-damaged colon epithelial cells were also shown to raise inflammation in macrophages via activating the STING pathway, but the effect disappeared after the removal of exosomal dsDNA. These findings were further confirmed in STING-deficient mice and macrophages. STING deficiency significantly ameliorated colitis. Besides, potential therapeutic effects of GW4869, an inhibitor of EVs release were assessed. The application of GW4869 successfully ameliorated murine colitis by inhibiting STING activation. In conclusion, exosomal dsDNA was found to promote intestinal inflammation via activating the STING pathway in macrophages and act as a potential mechanistic biomarker and therapeutic target of CD.
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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.