ArticleThe Journal of clinical investigation2020
Complement-activated interferon-γ-primed human endothelium transpresents interleukin-15 to CD8+ T cells.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- CD8Nature reviews. Cardiology · 2026Review
- Organelle stress in NLRP3 inflammasome: a central mediator of neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Pathogenesis of Chronic Rejection: Graft Endothelial Cell Trans-presentation of IL-15 Connects Alloantibody- and Cell-Mediated Steps in Allograft Vasculopathy.Results and problems in cell differentiation · 2026Review
- Functional Roles of the Complement Immune System in Cardiac Inflammation and Hypertrophy.International journal of molecular sciences · 2025Review
- Canonical and non-canonical roles of complement in atherosclerosis.Nature reviews. Cardiology · 2024Review
- IL-1β Induces Human Endothelial Surface Expression of IL-15 by Relieving let-7c-3p Suppression of Protein Translation.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- NIK Is a Mediator of Inflammation and Intimal Hyperplasia in Endothelial Denudation-Induced Vascular Injury.International journal of molecular sciences · 2024Article
- Translating B cell immunology to the treatment of antibody-mediated allograft rejection.Nature reviews. Nephrology · 2024Review
- IL-15 in T-Cell Responses and Immunopathogenesis.Immune network · 2024Review
- p40 homodimers bridge ischemic tissue inflammation and heterologous alloimmunity in mice via IL-15 transpresentation.The Journal of clinical investigation · 2024Article
- The Transplant Bellwether: Endothelial Cells in Antibody-Mediated Rejection.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- JAKinibs prevent persistent, IFNγ-autonomous endothelial cell inflammation and immunogenicity.American journal of physiology. Cell physiology · 2023Article
- A ZFYVE21-Rubicon-RNF34 signaling complex promotes endosome-associated inflammasome activity in endothelial cells.Nature communications · 2023Article
- Nucleic Acid Delivery to the Vascular Endothelium.Molecular pharmaceutics · 2022Review
- Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications.Nature communications · 2022Article
- Activation and regulation of alloreactive T cell immunity in solid organ transplantation.Nature reviews. Nephrology · 2022Review
- Membrane attack complexes, endothelial cell activation, and direct allorecognition.Frontiers in immunology · 2022Review
- Cardiac allograft vasculopathy: current review and future research directions.Cardiovascular research · 2021Review
- Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Alloantibodies in presensitized transplant candidates deposit complement membrane attack complexes (MACs) on graft endothelial cells (ECs), increasing risk of CD8+ T cell-mediated acute rejection. We recently showed that human ECs endocytose MACs into Rab5+ endosomes, creating a signaling platform that stabilizes NF-κB-inducing kinase (NIK) protein. Endosomal NIK activates both noncanonical NF-κB signaling to synthesize pro-IL-1β and an NLRP3 inflammasome to process and secrete active IL-1β. IL-1β activates ECs, increasing recruitment and activation of alloreactive effector memory CD4+ T (Tem) cells. Here, we report that IFN-γ priming induced nuclear expression of IL-15/IL-15Rα complexes in cultured human ECs and that MAC-induced IL-1β stimulated translocation of IL-15/IL-15Rα complexes to the EC surface in a canonical NF-κB-dependent process in which IL-15/IL-15Rα transpresentation increased activation and maturation of alloreactive CD8+ Tem cells. Blocking NLRP3 inflammasome assembly, IL-1 receptor, or IL-15 on ECs inhibited the augmented CD8+ Tem cell responses, indicating that this pathway is not redundant. Adoptively transferred alloantibody and mouse complement deposition induced IL-15/IL-15Rα expression by human ECs lining human coronary artery grafts in immunodeficient mice, and enhanced intimal CD8+ T cell infiltration, which was markedly reduced by inflammasome inhibition, linking alloantibody to acute rejection. Inhibiting MAC signaling may similarly limit other complement-mediated pathologies.
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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.