Actin dynamics is essential for T cell development. We show here that cofilin1 is the key molecule for controlling actin filament turnover in this process. Mice with specific depletion of cofilin1 in thymocytes showed increased steady state levels of actin filaments, and associated alterations in the pattern of thymocyte migration and adhesion. Our data suggest that cofilin1 is controlling oscillatory F-actin changes, a parameter that influences the migration pattern in a 3-D environment. In a collagen matrix, cofilin1 controls the speed and resting intervals of migrating thymocytes. Cofilin1 was not involved in thymocyte proliferation, cell survival, apoptosis, or surface receptor trafficking. However, in cofilin1 mutant mice impaired adhesion and migration resulted in a specific block of thymocyte differentiation from CD4/CD8 double positive thymocytes towards CD4 and CD8 single positive cells. Our data suggest that tuning of the dwelling time of thymocytes in the thymic niches is tightly controlled by cofilin1 and essential for positive selection during T cell differentiation. We describe a novel role of cofilin1 in the physiological context of migration dependent cell differentiation.

中文翻译：

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Cofilin1 驱动的肌动蛋白动力学控制胸腺细胞的迁移，对于胸腺的正选择至关重要。

肌动蛋白动力学对于 T 细胞发育至关重要。我们在此表明​​，cofilin1 是在此过程中控制肌动蛋白丝周转的关键分子。胸腺细胞中 cofilin1 特异性缺失的小鼠表现出肌动蛋白丝的稳态水平增加，以及胸腺细胞迁移和粘附模式的相关改变。我们的数据表明，cofilin1 正在控制 F-肌动蛋白的振荡变化，这是一个影响 3D 环境中迁移模式的参数。在胶原蛋白基质中，cofilin1 控制胸腺细胞迁移的速度和休息间隔。Cofilin1 不参与胸腺细胞增殖、细胞存活、细胞凋亡或表面受体运输。然而，在cofilin1突变小鼠中，粘附和迁移受损导致胸腺细胞从CD4/CD8双阳性胸腺细胞向CD4和CD8单阳性细胞的分化受到特定阻碍。我们的数据表明，胸腺细胞在胸腺微环境中停留时间的调节受到 cofilin1 的严格控制，并且对于 T 细胞分化过程中的正选择至关重要。我们描述了 cofilin1 在迁移依赖性细胞分化的生理背景中的新作用。