{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Li Y"],"funding":["NCRR NIH HHS","NCI NIH HHS"],"pagination":["2740-51"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2720133"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8(6)"],"pubmed_abstract":["Invariant NKT cells are a hybrid cell type of Natural Killer cells and T cells, whose development is dependent on thymic positive selection mediated by double positive thymocytes through their recognition of natural ligands presented by CD1d, a nonpolymorphic, non-MHC, MHC-like antigen presenting molecule. Genetic evidence suggested that beta-glucosylceramide derived glycosphingolipids (GSLs) are natural ligands for NKT cells. N-butyldeoxygalactonojirimycin (NB-DGJ), a drug that specifically inhibits the glucosylceramide synthase, inhibits the endogenous ligands for NKT cells. Furthermore, we and others have found a beta-linked glycosphingolipid, isoglobotriaosylceramide (iGb3), is a stimulatory NKT ligand. The iGb3 synthase knockout mice have a normal NKT development and function, indicating that other ligands exist and remain to be identified. In this study, we have performed a glycosphingolipidomics study of mouse thymus, and studied mice mutants which are deficient in beta-hexosaminidase b or alpha-galactosidase A, two glycosidases that are up- and downstream agents of iGb3 turnover, respectively. Our mass spectrometry methods generated a first database for glycosphingolipids expressed in mouse thymus, which are specifically regulated by rate-limiting glycosidases. Among the identified thymic glycosphingolipids, only iGb3 is a stimulatory ligand for NKT cells, suggesting that large-scale fractionation, enrichment and characterization of minor species of glycosphingolipids are necessary for identifying additional ligands for NKT cells. Our results also provide early insights into cellular lipidomics studies, with a specific focus on the important immunological functions of glycosphingolipids."],"journal":["Journal of proteome research"],"pubmed_title":["Immunologic glycosphingolipidomics and NKT cell development in mouse thymus."],"pmcid":["PMC2720133"],"funding_grant_id":["P20 RR016459","P50 CA100632-04","P20 RR16459","R21 RR020355","P50 CA100632","R21 RR20355","1P50 CA100632-04"],"pubmed_authors":["Thapa P","Hsu FF","Li Y","Furukawa K","Kondo Y","Palcic MM","Wang PG","Hawke D","Zhou D","Weadge J","Adlercreutz D","Levery SB"],"additional_accession":[]},"is_claimable":false,"name":"Immunologic glycosphingolipidomics and NKT cell development in mouse thymus.","description":"Invariant NKT cells are a hybrid cell type of Natural Killer cells and T cells, whose development is dependent on thymic positive selection mediated by double positive thymocytes through their recognition of natural ligands presented by CD1d, a nonpolymorphic, non-MHC, MHC-like antigen presenting molecule. Genetic evidence suggested that beta-glucosylceramide derived glycosphingolipids (GSLs) are natural ligands for NKT cells. N-butyldeoxygalactonojirimycin (NB-DGJ), a drug that specifically inhibits the glucosylceramide synthase, inhibits the endogenous ligands for NKT cells. Furthermore, we and others have found a beta-linked glycosphingolipid, isoglobotriaosylceramide (iGb3), is a stimulatory NKT ligand. The iGb3 synthase knockout mice have a normal NKT development and function, indicating that other ligands exist and remain to be identified. In this study, we have performed a glycosphingolipidomics study of mouse thymus, and studied mice mutants which are deficient in beta-hexosaminidase b or alpha-galactosidase A, two glycosidases that are up- and downstream agents of iGb3 turnover, respectively. Our mass spectrometry methods generated a first database for glycosphingolipids expressed in mouse thymus, which are specifically regulated by rate-limiting glycosidases. Among the identified thymic glycosphingolipids, only iGb3 is a stimulatory ligand for NKT cells, suggesting that large-scale fractionation, enrichment and characterization of minor species of glycosphingolipids are necessary for identifying additional ligands for NKT cells. Our results also provide early insights into cellular lipidomics studies, with a specific focus on the important immunological functions of glycosphingolipids.","dates":{"release":"2009-01-01T00:00:00Z","publication":"2009 Jun","modification":"2025-04-22T21:53:06.915Z","creation":"2019-03-27T00:23:57Z"},"accession":"S-EPMC2720133","cross_references":{"pubmed":["19284783"],"doi":["10.1021/pr801040h"]}}