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细胞是自适应免疫系统的重要组成部分，它源自在称为胸腺的器官中分化的干细胞。根据它们表达的T细胞受体（TCR）类别，可以将T细胞广泛分为两个不同的谱系，T细胞和T细胞。这些谱系来自双重祖先。尽管有关T细胞开发所需的信号传导途径知之甚少，但这些相同信号通路在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途径的信号传导已被证明可以调节 - 细胞的发展。但是，尚不清楚在GD-胞菌细胞发育的背景下，需要哪种RAS活化剂家族，RAS鸟苷核苷酸释放蛋白（RASGRP）或RAS激活的七个（SOS）家族的儿子。来自美国和其他人的数据以及我们的初步数据表明，RASGRP1缺乏症在胸腺细胞发育中起着至关重要的作用。我们建议测试Rasgrp1是胸腺细胞发育和功能谱系规范的关键调节剂的假设。此外，我们将确定GD-T细胞发育的RASGRP1调控的基础机制。这些信息将证明这对于进一步了解细胞命运决策的分子调节的长期目标至关重要。