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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >WIP is critical for T cell responsiveness to IL-2
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WIP is critical for T cell responsiveness to IL-2

机译：WIP对于T细胞对IL-2的反应至关重要

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摘要

The Wiskott-Aldrich syndrome (WAS) interacting protein (WIP) stabilizes the WAS protein (WASP), the product of the gene mutated in WAS. WIP-deficient T cells have low WASP levels, limiting the usefulness of WIP KO mice in defining the role of WIP in T cell function. To define this role, we compared WIP/WASP double KO (DKO) mice to WASP KO mice on DO11.10 background. T cell development was normal in both strains, but peripheral T cell numbers were significantly decreased in DKO mice. WASP KO T cells proliferated and secreted IL-2 normally in response to OVA peptide (OVAp). In contrast, T cells from DKO mice proliferated poorly in response to OVAp in vitro, and cutaneous hapten hyper-sensitivity was deficient in these mice. DKO T cells up-regulated CD25 expression and secreted normal amounts of IL-2 after antigen stimulation, but had defective response to IL-2, evidenced by failure to further up-regulate CD25 expression, phosphorylate STAT5, and induce expression of STAT5-dependent genes. DKO, but not WASP KO, T cells had a disrupted subcortical actin cytoskel-eton and impaired actin polymerization after T cell antigen receptor (TCR) ligation. These results indicate that WIP is essential for IL-2 signaling and responsiveness in T cells, possibly because of its critical role in TCR-triggered actin cytoskeletal reorganization.
机译：Wiskott-Aldrich综合征（WAS）相互作用蛋白（WIP）使WAS突变的基因产物WAS蛋白（WASP）稳定。缺乏WIP的T细胞的WASP水平较低，从而限制了WIP KO小鼠在定义WIP在T细胞功能中的作用方面的有用性。为了定义该角色，我们在DO11.10背景下将WIP / WASP双KO（DKO）小鼠与WASP KO小鼠进行了比较。两种品系中T细胞发育均正常，但DKO小鼠的外周T细胞数量明显减少。 WASP KO T细胞正常应答OVA肽（OVAp）增殖并分泌IL-2。相反，来自DKO小鼠的T细胞在体外对OVAp的反应增殖较差，并且这些小鼠的皮肤半抗原超敏性不足。 DKO T细胞在抗原刺激后上调CD25表达并分泌正常量的IL-2，但对IL-2有缺陷的反应，这由未能进一步上调CD25表达，磷酸化STAT5和诱导STAT5依赖性表达所证明基因。 TKO，但不是WASP KO，T细胞在T细胞抗原受体（TCR）连接后，皮层下肌动蛋白细胞骨架被破坏，肌动蛋白聚合受损。这些结果表明，WIP对于T细胞中的IL-2信号传导和反应性至关重要，可能是因为其在TCR触发的肌动蛋白细胞骨架重组中起关键作用。

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    Severine Le Bras; Michel Massaad; Suresh Koduru; Lalit Kumar; Michiko K. Oyoshi; John Hartwig; Raif S. Geha;

  • 作者单位

    Division of Immunology, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115;

    Division of Immunology, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115;

    Division of Immunology, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115;

    Division of Immunology, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115;

    Division of Immunology, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115;

    Division of Experimental Medicine, Brigham and Women's Hospital, Boston, MA 02115;

    Division of Immunology, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115;

  • 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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