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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=711798
• 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, T cells and 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 T cells, the role of these same signaling pathways in T cell development is unclear. Furthermore, unlike most T cells, T cells possess the ability to rapidly produce cytokines. Signaling through the Ras pathway has been demonstrated to regulate the development of -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 thymocyte development. We propose to test the hypothesis that RasGRP1 is a critical regulator of thymocyte development and functional lineage specification. Furthermore, we will determine the mechanism underlying RasGRP1 regulation of gd-T cell development. This information will prove critical to further our long-term goal of understanding the molecular regulation of cell fate decisions.

T细胞是适应性免疫系统的重要组成部分，它来源于干细胞，干细胞在一个叫做胸腺的器官中分化。T细胞可以根据其表达的T细胞受体（TCR）的类别广泛地分为两种不同的谱系，T细胞和T细胞。这些血统来自一个双能祖先。虽然关于T细胞发育所需的信号传导途径已经知道很多，但这些相同的信号传导途径在T细胞发育中的作用尚不清楚。此外，与大多数T细胞不同，T细胞具有快速产生细胞因子的能力。通过Ras信号通路已被证明调节胸腺细胞的发育。然而，目前还不清楚哪一个家族的Ras激活剂，Ras鸟苷酸释放蛋白（RasGRP）或Son of Sevenless（Sos）家族是必需的Ras激活的背景下，Gd-胸腺细胞发育。我们和其他人发表的数据以及我们的初步数据表明，RasGRP 1缺陷在胸腺细胞发育中起着关键作用。我们建议测试的假设，RasGRP 1是胸腺细胞发育和功能谱系规范的关键调节。此外，我们将确定RasGRP 1调节gd-T细胞发育的机制。这些信息将被证明是至关重要的，进一步我们的长期目标，了解细胞命运的决定的分子调控。