IMMUNOLOGIC GLYCOSPHINGOLIPIDOMICS AND NKT CELL DEVELOPMENT IN MOUSE THYMUS

小鼠胸腺中的免疫糖鞘脂和 NKT 细胞发育

• 批准号: 8361402
• 负责人: Yu Li
• 金额: $ 0.4万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361402
• 关键词: Antigens; Cells; Ceramide glucosyltransferase; Development; Funding; Genetic; Glucosylceramides; Glycosphingolipids; Grant; Hybrid Cells; Immunologics; Knockout Mice; Ligands; Link; Mass Spectrum Analysis; Mediating; Mus; National Center for Research Resources; Natural Killer Cells; Pharmaceutical Preparations; Principal Investigator; Research; Research Infrastructure; Resources; Source; T-Lymphocyte; Thymus Gland; UDP-galactose beta-D-galactosyl-1,4-glycosylceramide alpha-1,3-galactosyltransferase; United States National Institutes of Health; biomedical resource; cell type; cost; isoglobotriaosylceramide; thymocyte

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 恒定NKT细胞是自然杀伤细胞和T细胞的混合细胞类型，其发育依赖于双阳性胸腺细胞通过识别CD1d（一种非多态性、非MHC、MHC样抗原）呈递的天然配体介导的胸腺正选择呈现分子。遗传证据表明，β-葡萄糖神经酰胺衍生的鞘糖脂 (GSL) 是 NKT 细胞的天然配体。 N-丁基脱氧半乳糖野尻霉素 (NB-DGJ) 是一种特异性抑制葡萄糖神经酰胺合酶的药物，可抑制 NKT 细胞的内源性配体。此外，我们和其他人发现了一种 β 连接的鞘糖脂，异球三糖神经酰胺 (iGb3)，是一种刺激性 NKT 配体。 iGb3合酶敲除小鼠具有正常的NKT发育和功能，表明其他配体存在且有待鉴定。