ArticleScientific reports2017
Notch Ligand DLL4 Alleviates Allergic Airway Inflammation via Induction of a Homeostatic Regulatory Pathway.
Article in Scientific reports, 2017. 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, 30 citations in OpenAlex.
- Tryptophan metabolism reprogramming regulates Th1/Th2 immune balance and inhibits mast cell activation.Amino acids · 2026Article
- Study on Potential Differentially Expressed Genes in Idiopathic Pulmonary Fibrosis by Bioinformatics and Next-Generation Sequencing Data Analysis.Biomedicines · 2023Article
- Short-chain fatty acids ameliorate allergic airway inflammation via sequential induction of PMN-MDSCs and Treg cells.The journal of allergy and clinical immunology. Global · 2023Article
- Study on the mechanism of PM2.5 affecting Th1/Th2 immune imbalance through the notch signaling pathway in asthmatic mice.Toxicology research · 2023Article
- Characterization of the Notch pathway in nasal polyps of patients with chronic rhinosinusitis: A pilot study.Physiological reports · 2022Article
- Nuclear receptor Nr1d1 alleviates asthma by abating GATA3 gene expression and Th2 cell differentiation.Cellular and molecular life sciences : CMLS · 2022Article
- Article
- Asthma in the Precision Medicine Era: Biologics and Probiotics.International journal of molecular sciences · 2021Review
- Critical Roles of Balanced T Helper 9 Cells and Regulatory T Cells in Allergic Airway Inflammation and Tumor Immunity.Journal of immunology research · 2021Review
- Therapeutic Targeting of Notch Signaling: From Cancer to Inflammatory Disorders.Frontiers in cell and developmental biology · 2021Review
- Transcriptomic changes during TGF-β-mediated differentiation of airway fibroblasts to myofibroblasts.Scientific reports · 2019Article
- Emodin Alleviates the Airway Inflammation of Cough Variant Asthma in Mice by Regulating the Notch Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Multi-Faceted Notch in Allergic Airway Inflammation.International journal of molecular sciences · 2019Review
- netDx: interpretable patient classification using integrated patient similarity networks.Molecular systems biology · 2019Article
- Notch Signaling Regulates Immune Responses in Atherosclerosis.Frontiers in immunology · 2019Review
- Notch ligand Delta-like 4 induces epigenetic regulation of Treg cell differentiation and function in viral infection.Mucosal immunology · 2018Article
- A novel reporter allele for monitoringBiology open · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notch is a pleiotropic signaling family that has been implicated in pathogenesis of allergic airway diseases; however, the distinct function of individual Notch ligands remains elusive. We investigated whether Notch ligands, Jagged1 and DLL4, exert differential effects in OVA-induced allergic asthma. We found that whilst Jagged1 inhibition mitigated Th2-dominated airway inflammation, blockage of DLL4 aggravated the Th2-mediated asthma phenotypes. Additionally, Jagged1 signaling blockage enhanced IL-17 production and neutrophilic airway infiltration. In vitro, exogenous Jagged1 induced Th2-skewed responses, whereas augmented DLL4 signaling displayed a dual role by promoting expansion of both Tregs and Th17. In vivo, DLL4 blockage impaired Treg differentiation which plausibly resulted in exaggerated asthma phenotypes. On the contrary, administration of DLL4-expressing antigen-presenting cells promoted endogenous Treg expansion and ameliorated the allergic responses. Therefore, whilst Jagged1 induces Th2-skewed inflammation, DLL4 elicits an essential self-regulatory mechanism via Treg-mediated pathway that counterbalances Jagged1-induced Th2 responses and facilitates resolution of the airway inflammation to restore homeostasis. These findings uncover a disparate function of Jagged1 and DLL4 in allergic airway diseases, hinting feasibility of Notch ligand-specific targeting in therapy of allergic airway diseases.
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