The Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53226, USA.
J Exp Med. 2010 Feb 15;207(2):309-18. doi: 10.1084/jem.20090880. Epub 2010 Feb 1.
Phospholipase Cgamma1 (PLCgamma1) is an important signaling effector of T cell receptor (TCR). To investigate the role of PLCgamma1 in T cell biology, we generated and examined mice with T cell-specific deletion of PLCgamma1. We demonstrate that PLCgamma1 deficiency affects positive and negative selection, significantly reduces single-positive thymocytes and peripheral T cells, and impairs TCR-induced proliferation and cytokine production, and the activation of ERK, JNK, AP-1, NFAT, and NF-kappaB. Importantly, PLCgamma1 deficiency impairs the development and function of FoxP3(+) regulatory T cells, causing inflammatory/autoimmune symptoms. Therefore, PLCgamma1 is essential for T cell development, activation, and tolerance.
磷酸脂酶 Cγ1(PLCγ1)是 T 细胞受体(TCR)的一个重要信号效应物。为了研究 PLCγ1 在 T 细胞生物学中的作用,我们构建并研究了 PLCγ1 基因在 T 细胞中特异性缺失的小鼠。我们证明 PLCγ1 缺失影响了 T 细胞的阳性和阴性选择,显著减少了单阳性胸腺细胞和外周 T 细胞,并损害了 TCR 诱导的增殖和细胞因子产生,以及 ERK、JNK、AP-1、NFAT 和 NF-κB 的激活。重要的是,PLCγ1 缺失损害了 FoxP3(+)调节性 T 细胞的发育和功能,导致炎症/自身免疫症状。因此,PLCγ1 对于 T 细胞的发育、激活和耐受是必需的。