Unraveling the functional implications of GWAS: how T cell protein tyrosine phosphatase drives autoimmune disease.
Unraveling the functional implications of GWAS: how T cell protein tyrosine phosphatase drives autoimmune disease.
复制标题
DOI：
10.1172/jci60001
复制
发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
J. Zikherman;A. Weiss
中科院分区：
文献类型：
--
作者：
J. Zikherman;A. Weiss
全基因组关联研究 (GWAS) 已发现大量与人类自身免疫性疾病相关的 SNP。然而，大多数这些遗传变异的功能后果仍不清楚。 T 细胞蛋白酪氨酸磷酸酶（TCPTP，由 PTPN2 编码）是一种 JAK/STAT 和生长因子受体磷酸酶，GWAS 已将其与 1 型糖尿病、类风湿性关节炎和克罗恩病的发病机制联系起来。在本期 JCI 中，Wiede 及其同事生成了 TCPTP 的 T 细胞特异性缺失，并确定了这种磷酸酶作为 TCR 信号传导负调节因子的新作用。这些数据提供了关于 GWAS 中鉴定的非编码 PTPN2 SNP 如何驱动人类自身免疫性疾病的新见解。
Genome-wide association studies (GWAS) have identified a large number of SNPs that are linked to human autoimmune diseases. However, the functional consequences of most of these genetic variations remain undefined. T cell protein tyrosine phosphatase (TCPTP, which is encoded by PTPN2) is a JAK/STAT and growth factor receptor phosphatase that has been linked to the pathogenesis of type 1 diabetes, rheumatoid arthritis, and Crohn's disease by GWAS. In this issue of the JCI, Wiede and colleagues have generated a T cell-specific deletion of TCPTP and identified a novel role for this phosphatase as a negative regulator of TCR signaling. These data provide new insight as to how noncoding PTPN2 SNPs identified in GWAS could drive human autoimmune diseases.