ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Notch ligand delta-like 4 blockade alleviates experimental autoimmune encephalomyelitis by promoting regulatory T cell development.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 88 citations in OpenAlex.
- S3I-201, a STAT3 Inhibitor, Inhibits Proinflammatory Mediator Signalling in CD19 and CD45R/B220 Cells in a Mouse Model of Multiple Sclerosis.Cellular and molecular neurobiology · 2026Article
- Tryptophan metabolism reprogramming regulates Th1/Th2 immune balance and inhibits mast cell activation.Amino acids · 2026Article
- Exploring the Immunomodulatory Role of Forkhead Box Protein 3 (FOXP3) in the Pathophysiology of Neuropsychiatric Disorders.Molecular neurobiology · 2025Review
- Notch2-expressing CD4Cellular & molecular immunology · 2025Article
- Conversion of T Effector Cells Into T Regulatory Cells in Type 1 Diabetes/Latent Autoimmune Diabetes of Adults by Inhibiting eIF5A and Notch Pathways.ImmunoTargets and therapy · 2025Article
- Notch Signaling in Central Nervous System: From Cellular Development to Multiple Sclerosis Disease.Current neuropharmacology · 2024Review
- Delta- like ligand 4- expressing macrophages and human diseases: Insights into pathophysiology and therapeutic opportunities.Heliyon · 2023Review
- The potential value of Notch1 and DLL1 in the diagnosis and prognosis of patients with active TB.Frontiers in immunology · 2023Article
- Metabolic regulation and function of T helper cells in neuroinflammation.Seminars in immunopathology · 2022Review
- Roles of Notch Signaling in the Tumor Microenvironment.International journal of molecular sciences · 2022Review
- A narrative review of the role of the Notch signaling pathway in rheumatoid arthritis.Annals of translational medicine · 2022Review
- Role of Notch2 pathway in mature B cell malignancies.Frontiers in oncology · 2022Review
- Neuronal Cell Adhesion Molecules May Mediate Neuroinflammation in Autism Spectrum Disorder.Frontiers in psychiatry · 2022Review
- Targeting the Notch Signaling Pathway in Chronic Inflammatory Diseases.Frontiers in immunology · 2021Review
- Immune Cell Plasticity Allows for Resetting of Phenotype From Effector to Regulator With Combined Inhibition of Notch/eIF5A Pathways.Frontiers in cell and developmental biology · 2021Article
- Therapeutic Targeting of Notch Signaling: From Cancer to Inflammatory Disorders.Frontiers in cell and developmental biology · 2021Review
- Article
- NOTCH1 and DLL4 are involved in the human tuberculosis progression and immune response activation.Tuberculosis (Edinburgh, Scotland) · 2020Article
- Post-Developmental Roles of Notch Signaling in the Nervous System.Biomolecules · 2020Review
- Notch 1 Is Involved in CD4Frontiers in cellular and infection microbiology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Notch signaling pathway plays an important role in T cell differentiation. Delta-like ligand (Dll)4, one of five known Notch ligands, has been implicated in regulating Th2 cell differentiation in animal models of human diseases. However, the role of Dll4 in Th1/Th17-mediated autoimmune diseases remains largely unknown. Using an anti-Dll4 blocking mAb, we show that neutralizing Dll4 during the induction phase of experimental autoimmune encephalomyelitis in C57BL/6 mice significantly increased the pool of CD4(+)Foxp3(+) regulatory T cells (Treg) in the periphery and in the CNS, and decreased the severity of clinical disease and CNS inflammation. Dll4 blockade promoted induction of myelin-specific Th2/Treg immune responses and impaired Th1/Th17 responses compared with IgG-treated mice. In vitro, we show that signaling with recombinant Dll4 inhibits the TGF-β-induced Treg development, and inhibits Janus kinase 3-induced STAT5 phosphorylation, a transcription factor known to play a key role in Foxp3 expression and maintenance. Depletion of natural Treg using anti-CD25 Ab reversed the protective effects of anti-Dll4 Ab. These findings outline a novel role for Dll4-Notch signaling in regulating Treg development in EAE, making it an encouraging target for Treg-mediated immunotherapy in autoimmune diseases, such as multiple sclerosis.
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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.