Trial reportJournal of Crohn's & colitis2020
The TLR9 Agonist Cobitolimod Induces IL10-Producing Wound Healing Macrophages and Regulatory T Cells in Ulcerative Colitis.
Trial report in Journal of Crohn's & colitis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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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.
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Who cites it
45 citing papers in PubMed, 71 citations in OpenAlex.
- TLR4 maintains Treg-mediated protection against adverse outcomes in a model of hepatic surgical stress.The Journal of clinical investigation · 2026Article
- Advances in the Treatment of Ulcerative Colitis-From Conventional Therapies to Targeted Biologics and Small Molecules.International journal of molecular sciences · 2026Review
- Immunometabolic control of macrophage plasticity in wound healing: mechanistic insights and therapeutic opportunities.Frontiers in immunology · 2026Review
- Dimethyl itaconate suppresses dendritic cell and CD8BMC medicine · 2025Article
- Neuroimmune interactions in inflammatory bowel disease: Role of intestinal macrophages and the cholinergic pathway.World journal of gastroenterology · 2025Review
- Research Progress on the Relationship Between the Intestinal Barrier and Macrophages.Current issues in molecular biology · 2025Review
- Recent advances in the therapeutics and modes of action of a range of agents used to treat ulcerative colitis and related inflammatory conditions.Inflammopharmacology · 2025Review
- Association between Toll-like receptor 9 signaling defect and developing post-infectious irritable bowel syndrome.Frontiers in immunology · 2025Article
- Article
- The Role of Breast Milk Cell-Free DNA in the Regulation of the Neonatal Immune Response.Nutrients · 2024Review
- Tofacitinib for ulcerative colitis: A promising treatment option.World journal of gastroenterology · 2024Article
- Review
- Potential of using an engineered indole lactic acid producing Escherichia coli Nissle 1917 in a murine model of colitis.Scientific reports · 2024Article
- Rujin Jiedu decoction protects against influenza virus infection by modulating gut microbiota.Heliyon · 2024Article
- The Mechanisms of Adipose Stem Cell-Derived Exosomes Promote Wound Healing and Regeneration.Aesthetic plastic surgery · 2024Review
- Triad3A-Mediated K48-Linked ubiquitination and degradation of TLR9 impairs mitochondrial bioenergetics and exacerbates diabetic cardiomyopathy.Journal of advanced research · 2024Article
- Toll-like receptors in health and disease.MedComm · 2024Review
- Endoplasmic reticulum stress interferes with the development of type 1 regulating T cells.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Identification and preliminary validation of biomarkers associated with mitochondrial and programmed cell death in pre-eclampsia.Frontiers in immunology · 2024Article
- Hydrogel loaded with exosomes from WhartonZhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023Article
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsThe topically applied Toll-like receptor 9 [TLR9] agonist cobitolimod is a first-in-class DNA-based oligonucleotide with demonstrated therapeutic efficacy in clinical trials with ulcerative colitis [UC] patients. We here characterized its anti-inflammatory mechanism in UC.
methodsLuminal cobitolimod administration was evaluated in an experimental dextran sodium sulfate [DSS]-induced colitis model. Cultured blood and mucosal cells from UC patients were treated with cobitolimod and analysed via microarray, quantitative real-time PCR, ELISA and flow cytometry. Intestinal slides of cobitolimod-treated UC patients were analysed by immunohistochemistry.
resultsCobitolimod administration markedly suppressed experimental colitis activity, and microarray analyses demonstrated mucosal IL10 upregulation and suppression of IL17 signalling pathways. Cobitolimod treatment was associated with significant induction of mucosal IL10+Tr1 and Treg cells and suppression of Th17 cells. TLR9 knockout mice indicated that cobitolimod requires TLR9 signalling for IL10 induction. In UC patients, mucosal TLR9 levels correlated with severity of inflammation. Cobitolimod inhibited IL17A and IL17F, but increased IL10 and FoxP3 expression in cultured intestinal UC T cells. Cobitolimod-mediated suppression of intestinal IL17+T cells was abrogated by IL10 blockade. Furthermore, cobitolimod led to heightened IL10 production by wound healing macrophages. Immunohistochemistry in intestinal biopsies of cobitolimod-treated UC patients indicated increased presence of IL10+mononuclear and regulatory T cells, as well as reduction of IL17+cells.
conclusionActivation of TLR9 via cobitolimod might represent a novel therapeutic approach in UC, as it suppresses Th17 cells and induces anti-inflammatory IL10+macrophages and regulatory T cells, thereby modifying the dysregulated intestinal cytokine balance. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.
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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.