Defective thymic output in WAS patients is associated with abnormal actin organization.
Defective thymic output in WAS patients is associated with abnormal actin organization.
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WAS 患者的胸腺输出缺陷与肌动蛋白组织异常有关。
DOI：
10.1038/s41598-017-12345-z
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发表时间：
2017-09-20
影响因子：
4.6
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Li W;Sun X;Wang J;Zhao Q;Dai R;Wang Y;Zhou L;Westerberg L;Ding Y;Zhao X;Liu C
Wiskott-Aldrich 综合征蛋白 (WASp) 是肌动蛋白细胞骨架的关键调节因子。 T 细胞功能缺陷是 Wiskott-Aldrich 综合征 (WAS) 患者免疫缺陷的主要原因。 T细胞起源于骨髓并在胸腺中发育，然后迁移到外周组织。 TCR切除环（TREC）稳定存在于胸腺输出细胞中，可用作胸腺输出的分子标记。我们发现，与HC相比，经典WAS患者的CD8+ T幼稚细胞显着减少，经典WAS和X连锁血小板减少症（XLT）患者的TREC显着减少。 WAS (KO) 小鼠中的 TREC 也减少了。这些表明胸腺输出缺陷是 WAS 患者 T 细胞淋巴细胞减少的部分原因。然而，胸腺输出缺陷与肌动蛋白组织之间的相关性仍然难以捉摸。我们发现，与有或没有刺激的 HC 相比，WAS 和 XLT 患者的 T 细胞中 F-肌动蛋白的亚细胞位置和水平都发生了变化。我们的研究表明，WASp 在胸腺输出中发挥着关键作用，这与 T 细胞中 F-肌动蛋白的亚细胞位置和水平高度相关。
Wiskott-Aldrich syndrome protein (WASp) is a key regulator of the actin cytoskeleton. Defective T - cell function is a major cause for immune deficiency in Wiskott-Aldrich syndrome (WAS) patients. T cells originate in the bone marrow and develop in the thymus, and then migrate to peripheral tissues. TCR excision circles (TRECs) present in thymic output cells stably, which is used as a molecular marker for thymic output. We found that CD8+ T naïve cells of classic WAS patients were significantly reduced, and TRECs in patients with classic WAS and X-linked thrombocytopenia (XLT) dramatically decreased compared with that of HCs. TRECs were also reduced in WAS (KO) mice. These suggest that defective thymic output partially accounts for T cell lymphopenia in WAS patients. However, the correlation between the defect of thymic output and actin organization still remains elusive. We found that the subcellular location and the levels of of F-actin were altered in T cells from both WAS and XLT patients compared to that of HCs with or without stimulation. Our study shows that WASp plays a critical role in thymic output, which highly correlates with the subcellular location and level of F-actin in T cells.
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