ArticleJournal of immunology (Baltimore, Md. : 1950)2013
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.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- Identification of distinct cDC2 subpopulations that direct microbiota-specific T cell differentiation.bioRxiv : the preprint server for biology · 2025Article
- Early Notch signals from fibroblastic reticular cells program effector CD8+ T cell differentiation.The Journal of experimental medicine · 2025Article
- Notch signaling drives intestinal graft-versus-host disease in mice and nonhuman primates.Science translational medicine · 2023Article
- Article
- The Role of CTLA4 and Its Polymorphisms in Solid Organ and Haematopoietic Stem Cell Transplantation.International journal of molecular sciences · 2021Review
- Graft-versus-host disease depletes plasmacytoid dendritic cell progenitors to impair tolerance induction.The Journal of clinical investigation · 2021Article
- Therapeutic Targeting of Notch Signaling: From Cancer to Inflammatory Disorders.Frontiers in cell and developmental biology · 2021Review
- Notch signalling in T cell homeostasis and differentiation.Open biology · 2019Review
- Early Notch Signals Induce a Pathogenic Molecular Signature during Priming of Alloantigen-Specific Conventional CD4Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Dendritic Cell Regulation of Graft-Vs.-Host Disease: Immunostimulation and Tolerance.Frontiers in immunology · 2019Review
- Solid organ transplantation in the 21Annals of translational medicine · 2018Review
- Deficient humoral responses and disrupted B-cell immunity are associated with fatal SFTSV infection.Nature communications · 2018Article
- Bone marrow transplant-induced alterations in Notch signaling promote pathologic Th17 responses to γ-herpesvirus infection.Mucosal immunology · 2018Article
- Review
- NOTCH and Graft-Versus-Host Disease.Frontiers in immunology · 2018Review
- A Single Microorganism Epitope Attenuates the Development of Murine Autoimmune Arthritis: Regulation of Dendritic CellsFrontiers in immunology · 2018Article
- Notch Signaling as a Regulator of the Tumor Immune Response: To Target or Not To Target?Frontiers in immunology · 2018Review
- Fibroblastic niches prime T cell alloimmunity through Delta-like Notch ligands.The Journal of clinical investigation · 2017Article
- Notch Ligand Delta-like 4 Promotes Regulatory T Cell Identity in Pulmonary Viral Infection.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Notch Signaling and Immune Regulation in Alloimmunity.Current transplantation reports · 2016Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Graft-versus-host disease (GVHD) reflects an exaggerated inflammatory allogeneic T cell response in hosts receiving allogeneic hematopoietic stem cell transplantation (HSCT). Inhibition of pan-Notch receptor signaling in donor T cells causes reduction of GVHD. However, which Notch ligand(s) in what APCs is important for priming graft-versus-host reaction remains unknown. We demonstrate that δ-like ligand-4 (Dll4) and Dll4-positive (Dll4(high)) inflammatory dendritic cells (i-DCs) play important roles in eliciting allogeneic T cell responses. Host-type Dll4(high) i-DCs occurred in the spleen and intestine of HSCT mice during GVHD induction phase. These Dll4(high) i-DCs were CD11c(+)B220(+)PDCA-1(+), resembling plasmacytoid dentritic cells (pDCs) of naive mice. However, as compared with unstimulated pDCs, Dll4(high) i-DCs expressed higher levels of costimulatory molecules, Notch ligands Jagged1 and Jagged2, and CD11b, and produced more Ifnb and Il23 but less Il12. In contrast, Dll4-negative (Dll4(low)) i-DCs were CD11c(+)B220(-)PDCA-1(-), and had low levels of Jagged1. In vitro assays showed that Dll4(high) i-DCs induced significantly more IFN-γ- and IL-17-producing effector T cells (3- and 10-fold, respectively) than Dll4(low) i-DCs. This effect could be blocked by anti-Dll4 Ab. In vivo administration of Dll4 Ab reduced donor-alloreactive effector T cells producing IFN-γ and IL-17 in GVHD target organs, leading to reduction of GVHD and improved survival of mice after allogeneic HSCT. Our findings indicate that Dll4(high) i-DCs represent a previously uncharacterized i-DC population distinctive from steady state DCs and Dll4(low) i-DCs. Furthermore, Dll4 and Dll4(high) i-DCs may be beneficial targets for modulating allogeneic T cell responses, and could facilitate the discovery of human counterparts of mouse Dll4(high) i-DCs.
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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.