Role of RasGRP1 in regulating lymphocyte development and function

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(TCR)的表达类型，T细胞可以广泛地分为两个不同的谱系，即T细胞和T细胞。这些血统起源于一个具有双功能的祖先。虽然关于T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途径的信号已被证明调节胸腺细胞的发育。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缺陷在胸腺细胞发育中起着关键作用。我们建议检验RASGRP1是胸腺细胞发育和功能谱系规范的关键调节因子的假设。此外，我们还将确定RASGRP1调控gd-T细胞发育的机制。这些信息将被证明是推动我们理解细胞命运决定的分子调控的长期目标的关键。

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.