A CD26-Controlled Cell Surface Cascade for Regulation of T Cell Motility and Chemokine Signals1

A CD26-Controlled Cell Surface Cascade for Regulation of T Cell Motility and Chemokine Signals1
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用于调节 T 细胞运动和趋化因子信号的 CD26 控制的细胞表面级联1

DOI:
--
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发表时间:
2009
影响因子:
4.4
通讯作者:
K. Sundqvist
K. Sundqvist
中科院分区:
医学2区
文献类型:
--
作者:
Zhiwen Liu;M. Christensson;A. Forslöw;I. De Meester;K. Sundqvist

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趋化因子是细胞运输的关键调节因子,二肽基肽酶IV/CD26(CD26)使趋化因子失活。在这里,我们表明,与不经CD26处理的对照趋化因子相比,经CD26处理的趋化因子SDF 1 α/CXCL 12和RANTES/CCL 5是T淋巴细胞中血小板反应蛋白-1(TSP-1)通过CD26控制机制的细胞表面表达的有效诱导剂,并且TSP-1刺激脂蛋白受体相关蛋白/CD91的表达。因此,完整的TSP-1和TSP-1中序列的肽模拟物足以刺激CD91表达。趋化因子诱导的TSP-1和CD91的表达通过CD26和CXCL12和CCL5的抑制剂以及CD26的抑制剂刺激极化的细胞质通过TSP-1扩散和迁移来模拟。使用小干扰RNA沉默CD26或Ab诱导的CD26调节也增加TSP-1表达,并显著增强细胞质扩散和T细胞迁移。这些结果表明,CD26是通过抑制TSP-1表达的T细胞运动性的内源性抑制剂,并且趋化因子通过消除CD26依赖性抑制来刺激细胞极性和迁移。这表明T细胞运动性是由相互作用的细胞表面分子级联调节的。
Chemokines are key regulators of cell trafficking, and dipeptidyl peptidase IV/CD26 (CD26) inactivates chemokines. Here we show that the CD26-processed chemokines SDF1α/CXCL12 and RANTES/CCL5, in contrast to a control chemokine not processed by CD26, are potent inducers of cell surface expression of thrombospondin-1 (TSP-1) in T lymphocytes through a CD26-controlled mechanism and that TSP-1 stimulates expression of lipoprotein receptor related protein/CD91. Accordingly, intact TSP-1 and a peptide mimetic of a sequence in TSP-1 were sufficient to stimulate CD91 expression. The chemokine-induced expression of TSP-1 and CD91 was mimicked by inhibitors of CD26 and CXCL12 and CCL5 as well as inhibitors of CD26 stimulated polarized cytoplasmic spreading and migration through TSP-1. Silencing of CD26 using small interfering RNA or Ab-induced modulation of CD26 also increased TSP-1 expression and enhanced cytoplasmic spreading and T cell migration markedly. These results indicate that CD26 is an endogenous inhibitor of T cell motility through inhibition of TSP-1 expression and that chemokines stimulate cell polarity and migration through abrogation of the CD26-dependent inhibition. This suggests that T cell motility is regulated by a cascade of interacting cell surface molecules.
细胞附着血小板反应蛋白的多种机制。
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血小板反应蛋白的结构和功能特性。
DOI: --
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发表时间: 1993
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影响因子: --
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