ArticleThe Journal of clinical investigation2013
Blockade of individual Notch ligands and receptors controls graft-versus-host disease.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
99 citing papers in PubMed, 167 citations in OpenAlex.
- Phase 2 study of RO4929097, a gamma-secretase inhibitor, in metastatic melanoma: SWOG 0933.Cancer · 2015Trial
- Notch signaling at later stages of NK cell development enhances KIR expression and functional maturation.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Ciclopirox reprograms effector responses and modulates Notch1 activation in activated human T cells.iScience · 2026Article
- Homeostatic mature dendritic cells instruct fibroblast specialization via Notch2 signaling to establish T cell niches.Immunity · 2026Article
- Disrupting Notch signalling by a small molecule inhibiting dihydroorotate dehydrogenase activity.Scientific reports · 2026Article
- The Notch signaling pathway in regulating bone and cartilage homeostasis: novel insights into the pathogenesis and therapeutics of osteoarthritis.Cell communication and signaling : CCS · 2025Review
- Tumor-Associated Glycan Exploits Adenosine Receptor 2A Signaling to Facilitate Immune Evasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Early Notch signals from fibroblastic reticular cells program effector CD8+ T cell differentiation.The Journal of experimental medicine · 2025Article
- Splenic fibroblasts control marginal zone B cell movement and function via two distinct Notch2-dependent regulatory programs.Immunity · 2025Article
- The Impact of Cell-Intrinsic STAT6 Protein on Donor T Cell-Mediated Graft-Versus-Tumor Effect.International journal of molecular sciences · 2024Article
- Article
- Temporal dynamics and stoichiometry in human Notch signaling from Notch synaptic complex formation to nuclear entry of the Notch intracellular domain.Developmental cell · 2024Article
- Notch signaling in thyrocytes is essential for adult thyroid function and mammalian homeostasis.Nature metabolism · 2023Article
- Group 3 Innate Lymphoid Cells Exacerbate Lupus Nephritis by Promoting B Cell Activation in Kidney Ectopic Lymphoid Structures.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- SOHO State of the Art Updates and Next Questions | New Pathways and New Targets in PTCL: Staying on Target.Clinical lymphoma, myeloma & leukemia · 2023Review
- Notch signaling drives intestinal graft-versus-host disease in mice and nonhuman primates.Science translational medicine · 2023Article
- After Bone Marrow Transplantation, the Cell-Intrinsic Th2 Pathway Promotes Recipient T Lymphocyte Survival and Regulates Graft-versus-Host Disease.ImmunoHorizons · 2023Article
- Antibody blockade of Jagged1 attenuates choroidal neovascularization.Nature communications · 2023Article
- The Notch1/CD22 signaling axis disrupts Treg function in SARS-CoV-2-associated multisystem inflammatory syndrome in children.The Journal of clinical investigation · 2023Article
- Dissecting the regulatory network of transcription factors in T cell phenotype/functioning during GVHD and GVT.Frontiers in immunology · 2023Review
39 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
Graft-versus-host disease (GVHD) is the main complication of allogeneic bone marrow transplantation. Current strategies to control GVHD rely on global immunosuppression. These strategies are incompletely effective and decrease the anticancer activity of the allogeneic graft. We previously identified Notch signaling in T cells as a new therapeutic target for preventing GVHD. Notch-deprived T cells showed markedly decreased production of inflammatory cytokines, but normal in vivo proliferation, increased accumulation of regulatory T cells, and preserved anticancer effects. Here, we report that γ-secretase inhibitors can block all Notch signals in alloreactive T cells, but lead to severe on-target intestinal toxicity. Using newly developed humanized antibodies and conditional genetic models, we demonstrate that Notch1/Notch2 receptors and the Notch ligands Delta-like1/4 mediate all the effects of Notch signaling in T cells during GVHD, with dominant roles for Notch1 and Delta-like4. Notch1 inhibition controlled GVHD, but led to treatment-limiting toxicity. In contrast, Delta-like1/4 inhibition blocked GVHD without limiting adverse effects while preserving substantial anticancer activity. Transient blockade in the peritransplant period provided durable protection. These findings open new perspectives for selective and safe targeting of individual Notch pathway components in GVHD and other T cell-mediated human disorders.
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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.