ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Globosides but not isoglobosides can impact the development of invariant NKT cells and their interaction with dendritic cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Shiga toxin delivery in extracellular vesicles induces high mortality and severe kidney injury in a Gb3-dependent manner.PLoS pathogens · 2026Article
- Lipidomic scanning of self-lipids identifies headless antigens for natural killer T cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- CD1-mediated immune responses in mucosal tissues: molecular mechanisms underlying lipid antigen presentation system.Experimental & molecular medicine · 2023Review
- Glycolipids in Parkinson's disease: beyond neuronal function.FEBS open bio · 2023Review
- Lipid metabolic features of T cells in the Tumor Microenvironment.Lipids in health and disease · 2022Review
- The NKT cell TCR repertoire can accommodate structural modifications to the lipid and orientation of the terminal carbohydrate of iGb3.RSC advances · 2022Article
- Recent advances in the mass spectrometric analysis of glycosphingolipidome - A review.Analytica chimica acta · 2020Review
- TLR9-mediated dendritic cell activation uncovers mammalian ganglioside species with specific ceramide backbones that activate invariant natural killer T cells.PLoS biology · 2019Article
- Altered Lipid Tumor Environment and Its Potential Effects on NKT Cell Function in Tumor Immunity.Frontiers in immunology · 2019Review
- Lipid Antigen Presentation by CD1b and CD1d in Lysosomal Storage Disease Patients.Frontiers in immunology · 2019Article
- Immunometabolic Activation of Invariant Natural Killer T Cells.Frontiers in immunology · 2018Review
- CD1: A Singed Cat of the Three Antigen Presentation Systems.Archivum immunologiae et therapiae experimentalis · 2017Review
- Diastereomer-specific quantification of bioactive hexosylceramides from bacteria and mammals.Journal of lipid research · 2017Article
- From Lysosomal Storage Diseases to NKT Cell Activation and Back.International journal of molecular sciences · 2017Review
- Harnessing the Power of Invariant Natural Killer T Cells in Cancer Immunotherapy.Frontiers in immunology · 2017Review
- Critical Role for Very-Long Chain Sphingolipids in Invariant Natural Killer T Cell Development and Homeostasis.Frontiers in immunology · 2017Article
- Glucosylceramide Synthase Is Involved in Development of Invariant Natural Killer T Cells.Frontiers in immunology · 2017Article
- Chronic alcohol consumption enhances iNKT cell maturation and activation.Toxicology and applied pharmacology · 2015Article
- [Globosides as key players in the pathophysiology of Shiga toxin-associated acute kidney failure and Fabry disease].Der Pathologe · 2014Article
- Depletion of globosides and isoglobosides fully reverts the morphologic phenotype of Fabry disease.Cell and tissue research · 2014Article
Corrections and comments
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Authors and funding
15 authors at 10 institutions in 4 countries.
Funding
Abstract
Recognition of endogenous lipid Ag(s) on CD1d is required for the development of invariant NKT (iNKT) cells. Isoglobotrihexosylceramide (iGb3) has been implicated as this endogenous selecting ligand and recently suggested to control overstimulation and deletion of iNKT cells in α-galactosidase A-deficient (αGalA(-/-)) mice (human Fabry disease), which accumulate isoglobosides and globosides. However, the presence and function of iGb3 in murine thymus remained controversial. In this study, we generate a globotrihexosylceramide (Gb3)-synthase-deficient (Gb3S(-/-)) mouse and show that in thymi of αGalA(-/-)/Gb3S(-/-) double-knockout mice, which store isoglobosides but no globosides, minute amounts of iGb3 can be detected by HPLC. Furthermore, we demonstrate that iGb3 deficiency does not only fail to impact selection of iNKT cells, in terms of frequency and absolute numbers, but also does not alter the distribution of the TCR CDR 3 of iNKT cells. Analyzing multiple gene-targeted mouse strains, we demonstrate that globoside, rather than iGb3, storage is the major cause for reduced iNKT cell frequencies and defective Ag presentation in αGalA(-/-) mice. Finally, we show that correction of globoside storage in αGalA(-/-) mice by crossing them with Gb3S(-/-) normalizes iNKT cell frequencies and dendritic cell (DC) function. We conclude that, although detectable in murine thymus in αGalA(-/-)/Gb3S(-/-) mice, iGb3 does not influence either the development of iNKT cells or their interaction with peripheral DCs. Moreover, in αGalA(-/-) mice, it is the Gb3 storage that is responsible for the decreased iNKT cell numbers and impeded Ag presentation on DCs.
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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.