Restraint stress and stress hormones significantly impact T lymphocyte migration and function through specific alterations of the actin cytoskeleton
Restraint stress and stress hormones significantly impact T lymphocyte migration and function through specific alterations of the actin cytoskeleton
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DOI：
10.1016/j.bbi.2011.03.009
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发表时间：
2011-08-01
影响因子：
15.1
通讯作者：
Conrads, Thomas P.
中科院分区：
文献类型：
--
作者：
Flint, Melanie S.;Budiu, Raluca A.;Conrads, Thomas P.
压力触发了复杂的反应机制，旨在识别和适应体内平衡的扰动。免疫系统对应激反应强烈，尽管将应激和免疫介质（包括T淋巴细胞）联系起来的完整机制尚未完全了解。应激通过两个主要途径对免疫效应子发挥作用：交感神经-肾上腺-髓质途径和下丘脑-垂体-肾上腺途径，其调节适应性免疫和淋巴细胞迁移。在这份报告中，我们表明，压力通过释放应激激素诱导早期T细胞活化，并通过调节许多肌动蛋白调节蛋白极大地影响细胞骨架。特别是，蛋白质组学分析显示，许多关键肌动蛋白结合蛋白，包括膜突蛋白显着减少。虽然共聚焦显微镜显示，膜突蛋白和肌动蛋白均匀分布在静息T细胞的表面上，一个显着的极化和重新分配的膜突蛋白和肌动蛋白观察到以下处理应激激素与膜突蛋白定位在远极复合物。此外，膜突蛋白定位的改变和表达的最终降低伴随着CD 43的损失; CD 43是一种参与负调节T细胞活化的受体。总之，我们已经确定了一种新的分子机制，应激激素通过调节关键的细胞骨架和质膜因子对T细胞活化和迁移产生负面影响。(C)2011 Elsevier Inc. All rights reserved.
Stress triggers complex response mechanisms designed to recognize and adapt to perturbations in homeostasis. The immune system is highly responsive to stress, although the complete mechanisms linking stress and immune mediators including T lymphocytes, are not fully understood. Stress exerts its effects on immune effectors through two primary pathways: the sympathetic-adrenal-medullary pathway, and the hypothalamic-pituitary-adrenal pathway which modulate adaptive immunity and lymphocyte migration. In this report we show that stress via release of stress hormones induces early T cell activation and greatly impacts the cytoskeleton by modulating numerous actin-regulating proteins. In particular, proteomic profiling revealed significant decreases in numerous key actin-binding proteins including moesin. Although confocal microscopy showed that moesin and actin were uniformly distributed on the surface of resting T cells, a remarkable polarization and redistribution of moesin and actin was observed following treatment with stress hormones with moesin localizing at the distal pole complex. In addition, the alteration in moesin localization and eventual decrease in expression were accompanied by a loss of CD43; a receptor involved in negatively regulating T cell activation. In conclusion, we have defined a novel molecular mechanism whereby stress hormones negatively impact T cell activation and migration through regulation of key cytoskeletal and plasma membrane factors. (C) 2011 Elsevier Inc. All rights reserved.