Role of RasGRP1 in regulating lymphocyte development and function

RasGRP1 在调节淋巴细胞发育和功能中的作用

• 批准号: RGPIN-2017-05766
• 负责人: Baldwin, Troy
• 金额: $ 1.89万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629336
• 关键词: Role; RasGRP1; regulating; lymphocyte; development

T cells, an important component of the adaptive immune system, are derived from stem cells that undergo differentiation in an organ called the thymus. T cells can be broadly separated into two distinct lineages, αβ T cells and γδ T cells, based upon the class of T cell receptor (TCR) they express. These lineages arise from a bi-potent progenitor. While much is known regarding the signaling pathways required for development of αβ T cells, the role of these same signaling pathways in γδ T cell development is unclear. Furthermore, unlike most αβ T cells, γδ T cells possess the ability to rapidly produce cytokines. Signaling through the Ras pathway has been demonstrated to regulate the development of γδ-thymocytes. However, it is unclear which family of Ras activators, the Ras guanyl nucleotide releasing protein (RasGRP) or the Son of Sevenless (Sos) family is required for Ras activation in the context of gd-thymocyte development. Published data from us and others and our preliminary data suggest that RasGRP1 deficiency plays a critical role in γδ thymocyte development.

T细胞是获得性免疫系统的重要组成部分，它来自干细胞，这些干细胞在一种名为胸腺的器官中经历分化。根据T细胞受体表达的种类，T细胞可以广泛地分为两个不同的谱系，αβT细胞和γδT细胞。这些血统起源于一个具有双功能的祖先。虽然关于αβT细胞发育所需的信号通路已知很多，但这些相同的信号通路在γδT细胞发育中的作用尚不清楚。此外，与大多数αβT细胞不同，γδT细胞具有快速产生细胞因子的能力。已证实通过RAS信号通路调节γδ-胸腺细胞的发育。然而，目前还不清楚在gd胸腺细胞发育过程中，RAS激活剂家族中的哪一个家族，即RAS鸟苷释放蛋白(RasGRP)或Seven less家族的儿子(SOS)是RAS激活所必需的。我们和其他人发表的数据以及我们的初步数据表明，RASGRP1缺陷在γδ胸腺细胞发育中起着关键作用。