ArticleCirculation2019
Notch-1 Inhibition Promotes Immune Regulation in Transplantation Via Regulatory T Cell-Dependent Mechanisms.
Article in Circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 52 citations in OpenAlex.
- MLL1 Regulates T-Cell Phenotype via Notch Signaling During Abdominal Aortic Aneurysm Development.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Next-Generation regulatory T cell therapies: Translational considerations for inflammatory bowel disease.Human immunology · 2026Review
- Long-term vagus nerve stimulation synergized with rapamycin elicits neuroimmune modulation to prolong skin allograft survival.iScience · 2026Article
- Best practices in mouse models of skin transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Review
- Innovative approaches targeting innate immune cells to promote organ transplant tolerance.Frontiers in transplantation · 2026Review
- Notch3 destabilizes regulatory T cells to drive autoimmune neuroinflammation in multiple sclerosis.Immunity · 2025Article
- Tumor-Associated Glycan Exploits Adenosine Receptor 2A Signaling to Facilitate Immune Evasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Tolerogenic Therapies in Cardiac Transplantation.International journal of molecular sciences · 2025Review
- A biodegradable capacitive-coupling neurostimulator for wireless electroceutical treatment of inflammatory bowel diseases.Science advances · 2025Article
- 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
- The histone methyltransferase Mixed-lineage-leukemia-1 drives T cell phenotype via Notch signaling in diabetic tissue repair.JCI insight · 2024Article
- Review
- Regulatory T cells in dominant immunologic tolerance.The Journal of allergy and clinical immunology · 2024Review
- Genome-wide DNA methylation profiling of CD4BMC medical genomics · 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
- Tregs in transplantation tolerance: role and therapeutic potential.Frontiers in transplantation · 2023Review
- Review
- Ex vivo anchored PD-L1 functionally prevent in vivo renal allograft rejection.Bioengineering & translational medicine · 2022Article
- Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity.MedComm · 2022Review
- Notch signaling pathway: architecture, disease, and therapeutics.Signal transduction and targeted therapy · 2022Review
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Authors and funding
18 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundTransplantation is the treatment of choice for many patients with end-stage organ disease. Despite advances in immunosuppression, long-term outcomes remain suboptimal, hampered by drug toxicity and immune-mediated injury, the leading cause of late graft loss. The development of therapies that promote regulation while suppressing effector immunity is imperative to improve graft survival and minimize conventional immunosuppression. Notch signaling is a highly conserved pathway pivotal to T-cell differentiation and function, rendering it a target of interest in efforts to manipulate T cell-mediated immunity.
methodsWe investigated the pattern of Notch-1 expression in effector and regulatory T cells (Tregs) in both murine and human recipients of a solid-organ transplant. Using a selective human anti-Notch-1 antibody (aNotch-1), we examined the effect of Notch-1 receptor inhibition in full major histocompatibility complex-mismatch murine cardiac and lung transplant models, and in a humanized skin transplant model. On the basis of our findings, we further used a genetic approach to investigate the effect of selective Notch-1 inhibition in Tregs.
resultsWe observed an increased proportion of Tregs expressing surface and intracellular (activated) Notch-1 in comparison with conventional T cells, both in mice with transplants and in the peripheral blood of patients with transplants. In the murine cardiac transplant model, peritransplant administration of aNotch-1 (days 0, 2, 4, 6, 8, and 10) significantly prolonged allograft survival in comparison with immunoglobulin G-treated controls. Similarly, aNotch-1 treatment improved both histological and functional outcomes in the murine lung transplant model. The use of aNotch-1 resulted in a reduced proportion of both splenic and intragraft conventional T cells, while increasing the proportion of Tregs. Furthermore, Tregs isolated from aNotch-1-treated mice showed enhanced suppressive function on a per-cell basis, confirmed with selective Notch-1 deletion in Tregs (Foxp3
conclusionsOur data reveal a promising, clinically relevant approach for immune modulation in transplantation by selectively targeting Notch-1.
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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.