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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 不变的NKT细胞是一种自然杀伤细胞和T细胞的杂化细胞类型，其发育取决于双阳性胸腺细胞介导的胸腺阳性选择，它们通过识别CD1D呈现的自然配体，这是一种非甲状化，非MHC，非MHC，MHC样抗原分子。遗传证据表明，β-葡萄糖基酰胺衍生的糖磷脂（GSL）是NKT细胞的天然配体。 N-丁基氧基二甲二霉素（NB-DGJ）是一种专门抑制葡萄糖基酶合酶的药物，可抑制NKT细胞的内源性配体。此外，我们和其他人发现了β-连接的糖磷脂果质，异吞botriosylceramide（IGB3）是一种刺激性NKT配体。 IGB3合酶基因敲除小鼠具有正常的NKT发育和功能，表明存在其他配体并保持待鉴定。