ArticlePLoS biology2019
TLR9-mediated dendritic cell activation uncovers mammalian ganglioside species with specific ceramide backbones that activate invariant natural killer T cells.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Natural killer T cells in intracerebral hemorrhage: phase-dependent immune responses and therapeutic implications.Frontiers in immunology · 2026Review
- Global trends and frontiers in iNKT cells: a bibliometric and visualized analysis.Frontiers in immunology · 2025Article
- A modular chemoenzymatic cascade strategy for the structure-customized assembly of ganglioside analogs.Communications chemistry · 2024Article
- Role of ceramides in diabetic foot ulcers (Review).International journal of molecular medicine · 2023Review
- Novel lipid antigens for NKT cells in cancer.Frontiers in immunology · 2023Review
- Lipid metabolism and tumor immunotherapy.Frontiers in cell and developmental biology · 2023Review
- Antiviral activity of glucosylceramide synthase inhibitors in alphavirus infection of the central nervous system.Brain communications · 2023Article
- The biological role and immunotherapy of gangliosides and GD3 synthase in cancers.Frontiers in cell and developmental biology · 2023Review
- The NKT cell TCR repertoire can accommodate structural modifications to the lipid and orientation of the terminal carbohydrate of iGb3.RSC advances · 2022Article
- Immunolipidomics Reveals a Globoside Network During the Resolution of Pro-Inflammatory Response in Human Macrophages.Frontiers in immunology · 2022Article
- Review
- Diversification of CD1 Molecules Shapes Lipid Antigen Selectivity.Molecular biology and evolution · 2021Article
- Biological bases of cancer immunotherapy.Expert reviews in molecular medicine · 2021Article
- Liposomal Nanovaccine Containing α-Galactosylceramide and Ganglioside GM3 Stimulates Robust CD8Vaccines · 2021Article
- License to Kill: When iNKT Cells Are Granted the Use of Lethal Cytotoxicity.International journal of molecular sciences · 2020Review
- Tumor Lipids of Pediatric Papillary Renal Cell Carcinoma Stimulate Unconventional T Cells.Frontiers in immunology · 2020Article
- Bacterial immunogenic α-galactosylceramide identified in the murine large intestine: dependency on diet and inflammation.Journal of lipid research · 2019Article
- Altered Lipid Tumor Environment and Its Potential Effects on NKT Cell Function in Tumor Immunity.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
16 authors at 8 institutions in 6 countries.
Funding
Abstract
CD1d-restricted invariant natural killer T (iNKT) cells represent a heterogeneous population of lipid-reactive T cells that are involved in many immune responses, mediated through T-cell receptor (TCR)-dependent and/or independent activation. Although numerous microbial lipid antigens (Ags) have been identified, several lines of evidence have suggested the existence of relevant Ags of endogenous origin. However, the identification of their precise nature as well as the molecular mechanisms involved in their generation are still highly controversial and ill defined. Here, we identified two mammalian gangliosides-namely monosialoganglioside GM3 and disialoganglioside GD3-as endogenous activators for mouse iNKT cells. These glycosphingolipids are found in Toll-like receptor-stimulated dendritic cells (DC) as several species varying in their N-acyl fatty chain composition. Interestingly, their ability to activate iNKT cells is highly dependent on the ceramide backbone structure. Thus, both synthetic GM3 and GD3 comprising a d18:1-C24:1 ceramide backbone were able to activate iNKT cells in a CD1d-dependent manner. GM3 and GD3 are not directly recognized by the iNKT TCR and required the Ag presenting cell intracellular machinery to reveal their antigenicity. We propose a new concept in which iNKT cells can rapidly respond to pre-existing self-molecules after stress-induced structural changes in CD1d-expressing cells. Moreover, these gangliosides conferred partial protection in the context of bacterial infection. Thus, this report identified new biologically relevant lipid self-Ags for iNKT cells.
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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.