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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Opposing roles for RhoH GTPase during T-cell migration and activation
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Opposing roles for RhoH GTPase during T-cell migration and activation

机译：RhoH GTPase在T细胞迁移和激活过程中的相反作用

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摘要

T cells spend the majority of their time perusing lymphoid organs in search of cognate antigen presented by antigen presenting cells (APCs) and then quickly recirculate through the bloodstream to another lymph node. Therefore, regulation of a T-cell response is dependent upon the ability of cells to arrive in the correct location following chemokine gradients ("go" signal) as well as to receive appropriate T-cell receptor (TCR) activation signals upon cognate antigen recognition ("stop" signal). However, the mechanisms by which T cells regulate these go and stop signals remain unclear. We found that overexpression of the hematopoietic-specific RhoH protein in the presence of chemokine signals resulted in decreased Rap1-GTP and LFA-1 adhesiveness to ICAM-1, thus impairing T-cell chemotaxis; while in the presence of TCR signals, there were enhanced and sustained Rap1-GTP and LFA-1 activation as well as prolonged T:APC conjugates. RT-PCR analyses of activated CD4~+ T cells and live images of T-cell migration and immunological synapse (IS) formation revealed that functions of RhoH took place primarily at the levels of transcription and intracellular distribution. Thus, we conclude that RhoH expression provides a key molecular determinant that allows T cells to switch between sensing chemokine-mediated go signals and TCR-dependent stop signals.
机译：T细胞大部分时间都在仔细检查淋巴样器官，以寻找由抗原呈递细胞（APC）呈递的同源抗原，然后迅速通过血液循环到另一个淋巴结。因此，对T细胞应答的调节取决于细胞在趋化因子梯度后到达正确位置的能力（“ go”信号）以及在相关抗原识别后接收合适的T细胞受体（TCR）激活信号的能力。 （“停止”信号）。但是，尚不清楚T细胞调节这些信号的机制。我们发现在趋化因子信号的存在下，造血特异性RhoH蛋白的过表达导致Rap1-GTP和LFA-1对ICAM-1的粘附性降低，从而损害了T细胞的趋化性。而在存在TCR信号的情况下，Rap1-GTP和LFA-1活化增强并持续，并且T：APC偶联物延长。活化的CD4〜+ T细胞的RT-PCR分析以及T细胞迁移和免疫突触（IS）形成的实时图像显示，RhoH的功能主要发生在转录和细胞内分布的水平。因此，我们得出的结论是，RhoH表达提供了一个关键的分子决定因素，使T细胞可以在趋化因子介导的go信号和TCR依赖性终止信号之间进行切换。

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    Christina M. Baker; William A. Comrie; Young-Min Hyun; Hung-Li Chung; Christine A. Fedorchuk; Kihong Lim; Cord Brakebusch; James L McGrath; Richard E. Waugh; Martin Meier-Schellersheim; Minsoo Kim;

  • 作者单位

    Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, Rochester, NY 14642;

    Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, Rochester, NY 14642, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and Perelman School of Medicine at the Unniversity of Pennsylvania, Philadelphia PA, 19104;

    Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, Rochester, NY 14642;

    Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642;

    Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, Rochester, NY 14642;

    Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, Rochester, NY 14642;

    Department of Molecular Pathology, University of Copenhagen, 2200 Copenhagen N, Denmark;

    Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;

    Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642;

    Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;

    Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, Rochester, NY 14642;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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