ArticleJournal of immunology (Baltimore, Md. : 1950)2010
Notch ligand delta-like 4 regulates development and pathogenesis of allergic airway responses by modulating IL-2 production and Th2 immunity.
Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Jagged-1 Reduces Th2 Inflammation and Memory Cell Expansion in Allergic Airway Disease.ImmunoHorizons · 2023Article
- Multi-Faceted Notch in Allergic Airway Inflammation.International journal of molecular sciences · 2019Review
- Notch Signaling Orchestrates Helminth-Induced Type 2 Inflammation.Trends in immunology · 2019Review
- Notch signaling represents an important checkpoint between follicular T-helper and canonical T-helper 2 cell fate.Mucosal immunology · 2018Article
- Notch Ligand DLL4 Alleviates Allergic Airway Inflammation via Induction of a Homeostatic Regulatory Pathway.Scientific reports · 2017Article
- Notch Ligand Delta-like 4 Promotes Regulatory T Cell Identity in Pulmonary Viral Infection.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Notch Signaling in T Helper Cell Subsets: Instructor or Unbiased Amplifier?Frontiers in immunology · 2017Review
- DLL4Pharmacological research · 2016Review
- Systemic Expression of Notch Ligand Delta-Like 4 during Mycobacterial Infection Alters the T Cell Immune Response.Frontiers in immunology · 2016Article
- STAT5-induced lunatic fringe during Th2 development alters delta-like 4-mediated Th2 cytokine production in respiratory syncytial virus-exacerbated airway allergic disease.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Delta-like ligand 4 identifies a previously uncharacterized population of inflammatory dendritic cells that plays important roles in eliciting allogeneic T cell responses in mice.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Notch signaling and T-helper cells in EAE/MS.Clinical & developmental immunology · 2013Review
- Notch ligand delta-like 4-pretreated dendritic cells alleviate allergic airway responses by enhancing IL-10 production.PloS one · 2013Article
- STAT6-dependent and -independent mechanisms in Th2 polarization.European journal of immunology · 2012Review
- CD4+ T helper 2 cells--microbial triggers, differentiation requirements and effector functions.Immunology · 2011Review
- Notch and inflammatory T-cell response: new developments and challenges.Immunotherapy · 2011Review
- Notch ligand delta-like 4 blockade alleviates experimental autoimmune encephalomyelitis by promoting regulatory T cell development.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Activation of the canonical Notch pathways has been implicated in Th cell differentiation, but the role of specific Notch ligands in Th2-mediated allergic airway responses has not been completely elucidated. In this study, we show that delta-like ligand 4 (Dll4) was upregulated on dendritic cells in response to cockroach allergen. Blocking Dll4 in vivo during either the primary or secondary response enhanced allergen-induced pathogenic consequences including airway hyperresponsiveness and mucus production via increased Th2 cytokines. In vitro assays demonstrated that Dll4 regulates IL-2 in T cells from established Th2 responses as well as during primary stimulation. Notably, Dll4 blockade during the primary, but not the secondary, response increased IL-2 levels in lung and lymph node of allergic mice. The in vivo neutralization of Dll4 was associated with increased expansion and decreased apoptosis during the primary allergen sensitization. Moreover, Dll4-mediated Notch activation of T cells during primary stimulation in vitro increased apoptosis during the contraction/resting phase of the response, which could be rescued by exogenous IL-2. Consistent with the role for Dll4-mediated IL-2 regulation in overall T cell function, the frequency of IL-4-producing cells was also significantly altered by Dll4 both in vivo and in vitro. These data demonstrate a regulatory role of Dll4 both in initial Th2 differentiation and in Th2 cytokine production in established allergic responses.
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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.