Identification of a Novel Alternatively Spliced Form of Inflammatory Regulator SWAP-70-Like Adapter of T Cells.
Identification of a Novel Alternatively Spliced Form of Inflammatory Regulator SWAP-70-Like Adapter of T Cells.
复制标题
DOI：
10.1155/2017/1324735
复制
发表时间：
2017
影响因子：
2
通讯作者：
Tanaka Y
中科院分区：
文献类型：
--
作者：
Hashimoto M;Nagao JI;Ikezaki S;Tasaki S;Arita-Morioka KI;Narita Y;Cho T;Yuasa K;Altman A;Tanaka Y
初始 CD4+ T 细胞的激活导致效应 Th 细胞的几个不同亚群的发育，包括在过敏性炎症和蠕虫感染中发挥关键作用的 Th2 细胞。 SWAP-70 样 T 细胞适配器 (SLAT)，也称为 Def6 或 IBP，是小 GTP 酶的鸟嘌呤核苷酸交换因子，通过控制 Ca2+/NFAT 信号传导来调节 CD4+ T 细胞炎症反应。在这项研究中，我们鉴定了一种新的 SLAT 选择性剪接异构体，称为 SLAT2，它缺少由 Def6 基因的外显子 2-7 编码的区域。第二轮体外刺激后，SLAT2 在分化的 Th2 细胞中选择性表达，但在分化的 Th1、Th17 或调节性 T (Treg) 细胞中不表达。功能分析显示，SLAT2 与 SLAT 具有增强 T 细胞受体 (TCR-) 介导的 NFAT 激活和 IL-4 产生的能力，但无法增强 TCR 诱导的 ICAM-1 粘附。 Jurkat T 细胞中 SLAT2 或 SLAT 的异位表达导致不同形式的丝状伪足的表达，即分别是短丝状伪足和长丝状伪足。这些结果表明，调节 SLAT2 或 SLAT 蛋白表达可以在炎症免疫反应过程中的细胞因子产生和肌动蛋白重组中发挥关键作用。
Activation of naive CD4+ T cells results in the development of several distinct subsets of effector Th cells, including Th2 cells that play a pivotal role in allergic inflammation and helminthic infections. SWAP-70-like adapter of T cells (SLAT), also known as Def6 or IBP, is a guanine nucleotide exchange factor for small GTPases, which regulates CD4+ T cell inflammatory responses by controlling Ca2+/NFAT signaling. In this study, we have identified a novel alternatively spliced isoform of SLAT, named SLAT2, which lacks the region encoded by exons 2–7 of the Def6 gene. SLAT2 was selectively expressed in differentiated Th2 cells after the second round of in vitro stimulation, but not in differentiated Th1, Th17, or regulatory T (Treg) cells. Functional assays revealed that SLAT2 shared with SLAT the ability to enhance T cell receptor- (TCR-) mediated activation of NFAT and production of IL-4 but was unable to enhance TCR-induced adhesion to ICAM-1. Ectopic expression of SLAT2 or SLAT in Jurkat T cells resulted in the expression of distinct forms of filopodia, namely, short versus long ones, respectively. These results demonstrate that modulating either SLAT2 or SLAT protein expression could play critical roles in cytokine production and actin reorganization during inflammatory immune responses.