ArticleEBioMedicine2019
The Notch ligand DNER regulates macrophage IFNγ release in chronic obstructive pulmonary disease.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
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- Indole-3-Aldehyde alleviates lung inflammation in COPD through activating Aryl Hydrocarbon Receptor to inhibit HDACs/NF-κB/NLRP3 signaling pathways.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Macrophage Notch1 signaling modulates regulatory T cells via the TGFB axis in early MASLD.JHEP reports : innovation in hepatology · 2025Article
- M1 Macrophage is a Novel Potential Trigger for Endothelial Senescence: Role of Exosomal miR-155 Targeting SOCS1 Signal.Human mutation · 2025Article
- Identification of potential inflammation markers for outgrowth of cow's milk allergy.PloS one · 2025Article
- A Notch signaling pathway-related gene signature: Characterizing the immune microenvironment and predicting prognosis in hepatocellular carcinoma.Journal of translational internal medicine · 2024Article
- Potential Immune-Inflammatory Proteome Biomarkers for Guiding the Treatment of Patients with Primary Acute Angle-Closure Glaucoma Caused by COVID-19.Journal of proteome research · 2024Article
- Effect of glucocorticoids for the management of immune-related adverse events on outcome in melanoma patients treated with immunotherapy-a retrospective and biomarker study.Immuno-oncology technology · 2024Article
- Mechanism of Notch Signaling Pathway in Malignant Progression of Glioblastoma and Targeted Therapy.Biomolecules · 2024Review
- Screening COPD-Related Biomarkers and Traditional Chinese Medicine Prediction Based on Bioinformatics and Machine Learning.International journal of chronic obstructive pulmonary disease · 2024Article
- Biological Mechanism-based Neurology and Psychiatry: A BACE1/2 and Downstream Pathway Model.Current neuropharmacology · 2023Article
- Notch signaling pathway: architecture, disease, and therapeutics.Signal transduction and targeted therapy · 2022Review
- The Role of ABC Transporters in Lipid Metabolism and the Comorbid Course of Chronic Obstructive Pulmonary Disease and Atherosclerosis.International journal of molecular sciences · 2021Review
- Prognostic signature of lung adenocarcinoma based on stem cell-related genes.Scientific reports · 2021Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death worldwide with no curative therapy. A non-canonical Notch ligand, DNER, has been recently identified in GWAS to associate with COPD severity, but its function and contribution to COPD is unknown.
methodsDNER localisation was assessed in lung tissue from healthy and COPD patients, and cigarette smoke (CS) exposed mice. Microarray analysis was performed on WT and DNER deficient M1 and M2 bone marrow-derived macrophages (BMDM), and gene set enrichment undertaken. WT and DNER deficient mice were exposed to CS or filtered air for 3 day and 2 months to assess IFNγ-expressing macrophages and emphysema development. Notch and NFKB active subunits were quantified in WT and DNER deficient LPS-treated and untreated BMDM.
findingsImmunofluorescence staining revealed DNER localised to macrophages in lung tissue from COPD patients and mice. Human and murine macrophages showed enhanced DNER expression in response to inflammation. Interestingly, pro-inflammatory DNER deficient BMDMs exhibited impaired NICD1/NFKB dependent IFNγ signalling and reduced nuclear NICD1/NFKB translocation. Furthermore, decreased IFNγ production and Notch1 activation in recruited macrophages from CS exposed DNER deficient mice were observed, protecting against emphysema and lung dysfunction.
interpretationDNER is a novel protein induced in COPD patients and 6 months CS-exposed mice that regulates IFNγ secretion via non-canonical Notch in pro-inflammatory recruited macrophages. These results provide a new pathway involved in COPD immunity that could contribute to the discovery of innovative therapeutic targets.
fundingThis work was supported from the Helmholtz Alliance 'Aging and Metabolic Programming, AMPro'.
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