Role of RasGRP1 in regulating lymphocyte development and function

T细胞是适应性免疫系统的重要组成部分，它来自于胸腺器官中经过分化的干细胞。根据T细胞表达的T细胞受体（TCR）的类别，T细胞可以大致分为两个不同的谱系，T细胞和T细胞。这些世系起源于一个具有双重能力的祖先。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通路的信号传导已被证明可以调节-胸腺细胞的发育。然而，目前尚不清楚在gd胸腺细胞发育过程中，哪个Ras激活因子家族是Ras guanyl nucleotide release protein （RasGRP）或Son of seven - less （Sos）家族所需的Ras激活因子。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。我们建议验证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，我们将确定RasGRP1调控gd-T细胞发育的机制。这一信息对于进一步了解细胞命运决定的分子调控这一长期目标至关重要。

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.