Alexia Caillier, David Oleksyn, Deborah J Fowell, Jim Miller, Patrick W Oakes
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引用次数: 0
摘要
免疫细胞具有高度动态性,能够在具有不同生化和机械成分的环境中迁移。根据独立于整合素的假设,它们的迁移通常被定义为非膜性迁移。在这里,我们发现活化的原发性 Th1 T 细胞需要封闭和细胞外基质蛋白才能有效迁移。这种迁移是通过小而动态的局灶粘附介导的,局灶粘附由与典型间充质细胞局灶粘附相关的相同蛋白组成,如整合素、塔林和长链蛋白。此外,这些局灶粘附还定位在收缩牵引应力的部位,使 T 细胞能将自己拉过狭窄的空间。最后,我们发现 Th1 T 细胞会优先追随其他 T 细胞的轨迹,这表明这些粘附改变了细胞外基质,从而提供了额外的环境引导线索。这些结果不仅证明了非变形和间质迁移模式之间的界限模糊不清,而且证明了整合素介导的局灶粘附在 T 细胞运动中起着关键作用。
T cells use focal adhesions to pull themselves through confined environments.
Immune cells are highly dynamic and able to migrate through environments with diverse biochemical and mechanical compositions. Their migration has classically been defined as amoeboid under the assumption that it is integrin independent. Here, we show that activated primary Th1 T cells require both confinement and extracellular matrix proteins to migrate efficiently. This migration is mediated through small and dynamic focal adhesions that are composed of the same proteins associated with canonical mesenchymal cell focal adhesions, such as integrins, talin, and vinculin. These focal adhesions, furthermore, localize to sites of contractile traction stresses, enabling T cells to pull themselves through confined spaces. Finally, we show that Th1 T cells preferentially follow tracks of other T cells, suggesting that these adhesions modify the extracellular matrix to provide additional environmental guidance cues. These results demonstrate not only that the boundaries between amoeboid and mesenchymal migration modes are ambiguous, but that integrin-mediated focal adhesions play a key role in T cell motility.
期刊介绍:
The Journal of Cell Biology (JCB) is a comprehensive journal dedicated to publishing original discoveries across all realms of cell biology. We invite papers presenting novel cellular or molecular advancements in various domains of basic cell biology, along with applied cell biology research in diverse systems such as immunology, neurobiology, metabolism, virology, developmental biology, and plant biology. We enthusiastically welcome submissions showcasing significant findings of interest to cell biologists, irrespective of the experimental approach.