ArticleScience translational medicine2023
Notch signaling drives intestinal graft-versus-host disease in mice and nonhuman primates.
Article in Science translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The trial behind it
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Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- Spatiotemporal single-cell profiling reveals T cell clonal dynamics and phenotypic plasticity in human graft-versus-host disease.Nature immunology · 2026Article
- SPHK1 deficiency promotes intestinal homeostasis by ameliorating ER stress-induced gastrointestinal injury during murine graft-versus-host disease.Science China. Life sciences · 2026Article
- [Advances in the prevention and treatment of acute graft-versus-host disease with cellular and novel targeted immunotherapy].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Review
- Article
- Early Notch signals from fibroblastic reticular cells program effector CD8+ T cell differentiation.The Journal of experimental medicine · 2025Article
- Revisiting Tregs in cancer and beyond: immunological control and therapeutic potential.Frontiers in immunology · 2025Review
- Review
- Targeting the chemokines in acute graft-versus-host disease.Frontiers in immunology · 2024Review
- Distinct fibroblast functions associated with fibrotic and immune-mediated inflammatory diseases and their implications for therapeutic development.F1000Research · 2024Review
- Protective fibroblastic niches in secondary lymphoid organs.The Journal of experimental medicine · 2024Review
- Regulation of immune cell development, differentiation and function by stromal Notch ligands.Current opinion in cell biology · 2023Review
- Having it both ways: how STAT3 deficiency blocks graft-versus-host disease while preserving graft-versus-leukemia activity.The Journal of clinical investigation · 2023Article
Corrections and comments
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Authors and funding
31 authors at 9 institutions in 2 countries.
Funding
Abstract
Notch signaling promotes T cell pathogenicity and graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT) in mice, with a dominant role for the Delta-like Notch ligand DLL4. To assess whether Notch's effects are evolutionarily conserved and to identify the mechanisms of Notch signaling inhibition, we studied antibody-mediated DLL4 blockade in a nonhuman primate (NHP) model similar to human allo-HCT. Short-term DLL4 blockade improved posttransplant survival with durable protection from gastrointestinal GVHD in particular. Unlike prior immunosuppressive strategies tested in the NHP GVHD model, anti-DLL4 interfered with a T cell transcriptional program associated with intestinal infiltration. In cross-species investigations, Notch inhibition decreased surface abundance of the gut-homing integrin α4β7 in conventional T cells while preserving α4β7 in regulatory T cells, with findings suggesting increased β1 competition for α4 binding in conventional T cells. Secondary lymphoid organ fibroblastic reticular cells emerged as the critical cellular source of Delta-like Notch ligands for Notch-mediated up-regulation of α4β7 integrin in T cells after allo-HCT. Together, DLL4-Notch blockade decreased effector T cell infiltration into the gut, with increased regulatory to conventional T cell ratios early after allo-HCT. Our results identify a conserved, biologically unique, and targetable role of DLL4-Notch signaling in intestinal GVHD.
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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.