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: 8168806
• 负责人: Yu Li
• 金额: $ 1.13万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-10 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168806
• 关键词: Antigens; Cells; Ceramide glucosyltransferase; Computer Retrieval of Information on Scientific Projects Database; Development; Funding; Genetic; Glucosylceramides; Glycosphingolipids; Grant; Hybrid Cells; Immunologics; Institution; Knockout Mice; Ligands; Link; Mediating; Mus; Natural Killer Cells; Pharmaceutical Preparations; Research; Research Personnel; Resources; Source; T-Lymphocyte; Thymus Gland; UDP-galactose beta-D-galactosyl-1,4-glycosylceramide alpha-1,3-galactosyltransferase; United States National Institutes of Health; cell type; isoglobotriaosylceramide; thymocyte

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 恒定NKT细胞是自然杀伤细胞和T细胞的杂交细胞类型，其发育依赖于双阳性胸腺细胞介导的胸腺正选择，其通过识别由非多态性、非MHC、MHC样抗原呈递分子CD 1d呈递的天然配体。遗传证据表明，β-葡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，我们和其他人已经发现β-连接的鞘糖脂，isoglobotriaosylceramide（iGb 3），是一种刺激性NKT配体。iGb 3合酶敲除小鼠具有正常的NKT发育和功能，表明存在其他配体，并且仍有待鉴定。