ArticleThe Journal of clinical investigation2004
The clinical implication and molecular mechanism of preferential IL-4 production by modified glycolipid-stimulated NKT cells.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 199 citations in OpenAlex.
- Beyond α-GalCer: Medicinal Chemistry Insights Driving Structural Evolution of CD1d Ligands.Journal of medicinal chemistry · 2026Review
- Human NKT10 cells are enriched in cord-derived invariant natural killer T cells and mediate immune-regulation in a xenogeneic graft-versus-host disease model.Frontiers in immunology · 2026Article
- Can invariant Natural Killer T cells drive B cell fate? a look at the humoral response.Frontiers in immunology · 2025Review
- Optimizing iNKT-driven immune responses against cancer by modulating CD1d in tumor and antigen presenting cells.Clinical immunology (Orlando, Fla.) · 2024Review
- Efficacy and Safety of the Natural Killer T Cell-Stimulatory Glycolipid OCH-NCNP1 for Patients With Relapsing Multiple Sclerosis: Protocol for a Randomized Placebo-Controlled Clinical Trial.JMIR research protocols · 2024Article
- Keratinocyte-derived small extracellular vesicles supply antigens for CD1a-resticted T cells and promote their type 2 bias in the context of filaggrin insufficiency.Frontiers in immunology · 2024Article
- GARP on hepatic stellate cells is essential for the development of liver fibrosis.Journal of hepatology · 2023Article
- Glycolipids from the gut symbiontChemical science · 2023Article
- First-in-human clinical trial of the NKT cell-stimulatory glycolipid OCH in multiple sclerosis.Therapeutic advances in neurological disorders · 2023Article
- Unconventional T cells in brain homeostasis, injury and neurodegeneration.Frontiers in immunology · 2023Review
- Nanobody-mediated SPECT/CT imaging reveals the spatiotemporal expression of programmed death-ligand 1 in response to a CD8Theranostics · 2023Article
- Glycoconjugates: Synthesis, Functional Studies, and Therapeutic Developments.Chemical reviews · 2022Review
- Gut Microbiota-Derived Unconventional T Cell Ligands: Contribution to Host Immune Modulation.ImmunoHorizons · 2022Article
- Mucosal Vaccination With RecombinantFrontiers in immunology · 2022Article
- Cross Talk Between Natural Killer T and Dendritic Cells and Its Impact on T Cell Responses in Infections.Frontiers in immunology · 2022Review
- Thymic stromal lymphopoietin production in DN32.D3 invariant natural killer T (iNKT) cell line and primary mouse liver iNKT cells.Asia Pacific allergy · 2021Article
- Impaired lipid biosynthesis hinders anti-tumor efficacy of intratumoral iNKT cells.Nature communications · 2020Article
- Modulation of Immune Responses to Influenza A Virus Vaccines by Natural Killer T Cells.Frontiers in immunology · 2020Review
- 4"-O-Alkylated α-Galactosylceramide Analogues as iNKT-Cell Antigens: Synthetic, Biological, and Structural Studies.ChemMedChem · 2019Article
- NKT cells in liver diseases.Frontiers of medicine · 2018Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
OCH, a sphingosine-truncated analog of alpha-galactosylceramide (alphaGC), is a potential therapeutic reagent for a variety of Th1-mediated autoimmune diseases through its selective induction of Th2 cytokines from natural killer T (NKT) cells. We demonstrate here that the NKT cell production of IFN-gamma is more susceptible to the sphingosine length of glycolipid ligand than that of IL-4 and that the length of the sphingosine chain determines the duration of NKT cell stimulation by CD1d-associated glycolipids. Furthermore, IFN-gamma production by NKT cells requires longer T cell receptor stimulation than is required for IL-4 production by NKT cells stimulated either with immobilized mAb to CD3 or with immobilized "alphaGC-loaded" CD1d molecules. Interestingly, transcription of IFN-gamma but not that of IL-4 was sensitive to cycloheximide treatment, indicating the intrinsic involvement of de novo protein synthesis for IFN-gamma production by NKT cells. Finally, we determined c-Rel was preferentially transcribed in alphaGC-stimulated but not in OCH-stimulated NKT cells and was essential for IFN-gamma production by activated NKT cells. Given the dominant immune regulation by the remarkable cytokine production of ligand-stimulated NKT cells in vivo, in comparison with that of (antigen-specific) T cells or NK cells, the current study confirms OCH as a likely therapeutic reagent for use against Th1-mediated autoimmune diseases and provides a novel clue for the design of drugs targeting NKT cells.
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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.