ArticleThe Journal of experimental medicine2007
The Niemann-Pick type C2 protein loads isoglobotrihexosylceramide onto CD1d molecules and contributes to the thymic selection of NKT cells.
Article in The Journal of experimental medicine, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 100 citations in OpenAlex.
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- CD1 molecules: Beyond antigen presentation.Molecular immunology · 2024Review
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- Inherited Metabolic Disorders: From Bench to Bedside.Biomedicines · 2024Article
- Glycolipids in Parkinson's disease: beyond neuronal function.FEBS open bio · 2023Review
- CD1-mediated immune responses in mucosal tissues: molecular mechanisms underlying lipid antigen presentation system.Experimental & molecular medicine · 2023Review
- Leukocyte Imbalances in Mucopolysaccharidoses Patients.Biomedicines · 2023Article
- Polymer-based drug delivery systems under investigation for enzyme replacement and other therapies of lysosomal storage disorders.Advanced drug delivery reviews · 2023Review
- The Effect of Lipid Metabolism on CD4Mediators of inflammation · 2021Review
- Understanding and Treating Niemann-Pick Type C Disease: Models Matter.International journal of molecular sciences · 2020Review
- Lipid Antigen Presentation by CD1b and CD1d in Lysosomal Storage Disease Patients.Frontiers in immunology · 2019Article
- The lipid transfer protein Saposin B does not directly bind CD1d for lipid antigen loading.Wellcome open research · 2019Article
- The ins and outs of type I iNKT cell development.Molecular immunology · 2019Review
- Role of lipid transfer proteins in loading CD1 antigen-presenting molecules.Journal of lipid research · 2018Review
- Immunometabolic Activation of Invariant Natural Killer T Cells.Frontiers in immunology · 2018Review
- Differential Role of Cathepsins S and B In Hepatic APC-Mediated NKT Cell Activation and Cytokine Secretion.Frontiers in immunology · 2018Article
- Natural killer T cells in atherosclerosis.Nature reviews. Cardiology · 2017Review
- From Lysosomal Storage Diseases to NKT Cell Activation and Back.International journal of molecular sciences · 2017Review
- Reciprocal Crosstalk between Dendritic Cells and Natural Killer T Cells: Mechanisms and Therapeutic Potential.Frontiers in immunology · 2017Review
- The processing and presentation of lipids and glycolipids to the immune system.Immunological reviews · 2016Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The Niemann-Pick type C2 (NPC2) protein is a small, soluble, lysosomal protein important for cholesterol and sphingolipid transport in the lysosome. The immunological phenotype of NPC2-deficient mice was limited to an impaired thymic selection of Valpha14 natural killer T cells (NKT cells) and a subsequent reduction of NKT cells in the periphery. The remaining NKT cells failed to produce measurable quantities of interferon-gamma in vivo and in vitro after activation with alpha-galactosylceramide. In addition, thymocytes and splenocytes from NPC2-deficient mice were poor presenters of endogenous and exogenous lipids to CD1d-restricted Valpha14 hybridoma cells. Importantly, we determined that similar to saposins, recombinant NPC2 was able to unload lipids from and load lipids into CD1d. This transfer activity was associated with a dimeric form of NPC2, suggesting a unique mechanism of glycosphingolipid transfer by NPC2. Similar to saposin B, NPC2 dimers were able to load isoglobotrihexosylceramide (iGb3), the natural selecting ligand of NKT cells in the thymus, into CD1d. These observations strongly suggested that the phenotype observed in NPC2-deficient animals was directly linked to the efficiency of the loading of iGb3 into CD1d molecules expressed by thymocytes. This conclusion was supported by the rescue of endogenous and exogenous iGb3 presentation by recombinant NPC2. Thus, the loading of endogenous and exogenous lipids and glycolipids onto CD1d is dependent on various small, soluble lipid transfer proteins present in the lysosome.
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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.