ArticleThe Journal of experimental medicine2012
Dll4-Notch signaling in Flt3-independent dendritic cell development and autoimmunity in mice.
Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- Notch signaling inhibition attenuates epileptogenesis and hippocampal damage without altering mossy fiber sprouting in adolescent rats post-status epilepticus.Frontiers in molecular neuroscience · 2026Article
- 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
- Innate and adaptive immune abnormalities underlying autoimmune diseases: the genetic connections.Science China. Life sciences · 2023Review
- Innate immunity in latent autoimmune diabetes in adults.Diabetes/metabolism research and reviews · 2022Review
- Oral probiotic promotes indoleamine 2,3-dioxygenase- and TGF-β-Producing plasmacytoid dendritic cells to initiate protection against type 1 diabetes.Immunology letters · 2021Article
- 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
- Transient Depletion of Foxp3Frontiers in immunology · 2021Article
- Delta-like ligand 4-mediated Notch signaling controls proliferation of second heart field progenitor cells by regulating Fgf8 expression.Development (Cambridge, England) · 2020Article
- NOTCH1 and DLL4 are involved in the human tuberculosis progression and immune response activation.Tuberculosis (Edinburgh, Scotland) · 2020Article
- Multi-Faceted Notch in Allergic Airway Inflammation.International journal of molecular sciences · 2019Review
- Cellular immunological changes in patients with LADA are a mixture of those seen in patients with type 1 and type 2 diabetes.Clinical and experimental immunology · 2019Article
- Generating mouse models for biomedical research: technological advances.Disease models & mechanisms · 2019Review
- Autoimmune-Mediated Thymic Atrophy Is Accelerated but Reversible in RelB-Deficient Mice.Frontiers in immunology · 2018Article
- Article
- 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
- Notch Signaling and Alloreactivity.Transplantation · 2016Review
- Are Regulatory T Cells Defective in Type 1 Diabetes and Can We Fix Them?Journal of immunology (Baltimore, Md. : 1950) · 2016Review
- Targeting the Notch Pathway to Prevent Rejection.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2016Review
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
Abstract
Delta-like ligand 4 (Dll4)-Notch signaling is essential for T cell development and alternative thymic lineage decisions. How Dll4-Notch signaling affects pro-T cell fate and thymic dendritic cell (tDC) development is unknown. We found that Dll4 pharmacological blockade induces accumulation of tDCs and CD4(+)CD25(+)FoxP3(+) regulatory T cells (T(reg) cells) in the thymic cortex. Both genetic inactivation models and anti-Dll4 antibody (Ab) treatment promote de novo natural T(reg) cell expansion by a DC-dependent mechanism that requires major histocompatibility complex II expression on DCs. Anti-Dll4 treatment converts CD4(-)CD8(-)c-kit(+)CD44(+)CD25(-) (DN1) T cell progenitors to immature DCs that induce ex vivo differentiation of naive CD4(+) T cells into T(reg) cells. Induction of these tolerogenic DN1-derived tDCs and the ensuing expansion of T(reg) cells are Fms-like tyrosine kinase 3 (Flt3) independent, occur in the context of transcriptional up-regulation of PU.1, Irf-4, Irf-8, and CSF-1, genes critical for DC differentiation, and are abrogated in thymectomized mice. Anti-Dll4 treatment fully prevents type 1 diabetes (T1D) via a T(reg) cell-mediated mechanism and inhibits CD8(+) T cell pancreatic islet infiltration. Furthermore, a single injection of anti-Dll4 Ab reverses established T1D. Disease remission and recurrence are correlated with increased T(reg) cell numbers in the pancreas-draining lymph nodes. These results identify Dll4-Notch as a novel Flt3-alternative pathway important for regulating tDC-mediated T(reg) cell homeostasis and autoimmunity.
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What OpenQuestion holds
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.