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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Coordination of IL-7 receptor and T-cell receptor signaling by cell-division cycle 42 in T-cell homeostasis
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Coordination of IL-7 receptor and T-cell receptor signaling by cell-division cycle 42 in T-cell homeostasis

机译：T细胞稳态中细胞分裂周期42对IL-7受体和T细胞受体信号传导的协调作用

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摘要

T-cell homeostasis is essential for normal functioning of the immune system. IL-7 receptor (IL-7R) and T-cell receptor(TCR) signaling are pivotal for T-cell homeostatic regulation. The detailed mechanisms regulating T-cell homeostasis and how IL-7R and TCR signaling are coordinated are largely unknown. Here we demonstrate that T cell-specific deletion of cell-division cycle 42 (Cdc42) GTPase causes a profound loss of mature T cells. Deletion of Cdc42 leads to a markedly increased expression of growth factor indepen-dence-1 (Gfi-1) and represses expression of IL-7Ra. In the absence of Cdc42. aberrant ERK1/2 MAP kinase activity results in enhanced, TCR-mediated T-cell proliferation. In vivo reconstitution of effector-binding-defective Cdc42 mutants and the effector p21 protein-activated kinase 1 (PAK1) into Cdc42-deficient T cells showed that PAK1 is both necessary and sufficient for Cdc42-regulated T-cell homeostasis. Thus, T-cell homeostasis is maintained through a concerted regulation of Gfi-1-IL-7R-controlled cytokine responsiveness and ERK-mediated TCR signaling strength by the Cdc42-PAK1 signaling axis.
机译：T细胞稳态对于免疫系统的正常运转至关重要。 IL-7受体（IL-7R）和T细胞受体（TCR）信号对于T细胞稳态调节至关重要。调节T细胞稳态以及IL-7R和TCR信号如何协调的详细机制在很大程度上尚不清楚。在这里，我们证明细胞分裂周期42（Cdc42）GTPase的T细胞特异性缺失导致成熟T细胞的大量损失。 Cdc42的删除导致生长因子独立1（Gfi-1）的表达明显增加，并抑制IL-7Ra的表达。在没有Cdc42的情况下。错误的ERK1 / 2 MAP激酶活性导致增强的TCR介导的T细胞增殖。体内的效应结合缺陷的Cdc42突变体和效应子p21蛋白激活的激酶1（PAK1）重组为Cdc42缺陷的T细胞表明，PAK1对于Cdc42调节的T细胞稳态而言既必要又充分。因此，通过Cdc42-PAK1信号转导轴对Gfi-1-IL-7R控制的细胞因子反应性和ERK介导的TCR信号转导强度的协调调节，可以维持T细胞的稳态。

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    Fukun Guo; David Hildeman; Pulak Tripathi; Chinavenmeni S. Velu; H. Leighton Grimes; Yi Zheng;

  • 作者单位

    Divisions of Experirnental Hematology and Cancer Biology Children's Hospital Research Foundation, Cincinnati, OH 45229;

    rnDivisions of Immunobiology, Children's Hospital Research Foundation, Cincinnati, OH 45229;

    rnDivisions of Immunobiology, Children's Hospital Research Foundation, Cincinnati, OH 45229;

    rnDivisions of Immunobiology, Children's Hospital Research Foundation, Cincinnati, OH 45229;

    rnDivisions of Immunobiology, Children's Hospital Research Foundation, Cincinnati, OH 45229;

    rnDivisions of Experirnental Hematology and Cancer Biology Children's Hospital Research Foundation, Cincinnati, OH 45229;

  • 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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  • 正文语种 eng
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