ArticleJCI insight2017
Ceramide synthesis regulates T cell activity and GVHD development.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies.Nature communications · 2019Pooled it
- Lipid dysregulation after hematopoietic stem cell transplant.Haematologica · 2026Article
- Ceramide signaling in immunity: a molecular perspective.Lipids in health and disease · 2025Review
- Inhibition of CD38 enzyme activity on engrafted human immune cells enhances NAD+ metabolism and inhibits inflammation in anFrontiers in immunology · 2025Article
- Metabolic shifts during coffee consumption refresh the immune response: insight from comprehensive multiomics analysis.MedComm · 2024Article
- The integration of metabolic and proteomic data uncovers an augmentation of the sphingolipid biosynthesis pathway during T-cell differentiation.Communications biology · 2024Article
- Cancer immunometabolism: advent, challenges, and perspective.Molecular cancer · 2024Review
- Reduced Ceramides Are Associated with Acute Rejection in Liver Transplant Patients and Skin Graft and Hepatocyte Transplant Mice, Reducing Tolerogenic Dendritic Cells.Molecules and cells · 2023Article
- The heat shock protein Hsp27 controls mitochondrial function by modulating ceramide generation.Cell reports · 2023Article
- DISCERN: deep single-cell expression reconstruction for improved cell clustering and cell subtype and state detection.Genome biology · 2023Article
- Mass Spectrometry Detects Sphingolipid Metabolites for Discovery of New Strategy for Cancer Therapy from the Aspect of Programmed Cell Death.Metabolites · 2023Review
- Functional roles of sphingolipids in immunity and their implication in disease.Experimental & molecular medicine · 2023Review
- Orchestral role of lipid metabolic reprogramming in T-cell malignancy.Frontiers in oncology · 2023Review
- Human Alpha-1 Antitrypsin Attenuates ENaC and MARCKS and Lowers Blood Pressure in Hypertensive Diabetic db/db Mice.Biomolecules · 2022Article
- The druggable transcription factor Fli-1 regulates T cell immunity and tolerance in graft-versus-host disease.The Journal of clinical investigation · 2022Article
- Pretransplant Systemic Lipidomic Profiles in Allogeneic Stem Cell Transplant Recipients.Cancers · 2022Article
- Sphingolipids in embryonic development, cell cycle regulation, and stemness - Implications for polyploidy in tumors.Seminars in cancer biology · 2022Review
- Lipid metabolism in T cell signaling and function.Nature chemical biology · 2022Review
- Review
- Sphingolipid metabolism in T cell responses after allogeneic hematopoietic cell transplantation.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective immunotherapy for a variety of hematologic malignances, yet its efficacy is impeded by the development of graft-versus-host disease (GVHD). GVHD is characterized by activation, expansion, cytokine production, and migration of alloreactive donor T cells. Hence, strategies to limit GVHD are highly desirable. Ceramides are known to contribute to inflammation and autoimmunity. However, their involvement in T-cell responses to alloantigens is undefined. In the current study, we specifically characterized the role of ceramide synthase 6 (CerS6) after allo-HCT using genetic and pharmacologic approaches. We found that CerS6 was required for optimal T cell activation, proliferation, and cytokine production in response to alloantigen and for subsequent induction of GVHD. However, CerS6 was partially dispensable for the T cell-mediated antileukemia effect. At the molecular level, CerS6 was required for efficient TCR signal transduction, including tyrosine phosphorylation, ZAP-70 activation, and PKCθ/TCR colocalization. Impaired generation of C16-ceramide was responsible for diminished allogeneic T cell responses. Furthermore, targeting CerS6 using a specific inhibitor significantly reduced T cell activation in mouse and human T cells in vitro. Our study provides a rationale for targeting CerS6 to control GVHD, which would enhance the efficacy of allo-HCT as an immunotherapy for hematologic malignancies in the clinic.
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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.