Department of Immunopathology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
Nat Immunol. 2010 Jul;11(7):594-600. doi: 10.1038/ni.1885. Epub 2010 May 30.
The recirculation of leukocytes is essential for proper immune responses. However, the molecular mechanisms that regulate the entry of leukocytes into the lymphatics remain unclear. Here we show that plexin-A1, a principal receptor component for class III and class VI semaphorins, was crucially involved in the entry of dendritic cells (DCs) into the lymphatics. Additionally, we show that the semaphorin Sema3A, but not Sema6C or Sema6D, was required for DC transmigration and that Sema3A produced by the lymphatics promoted actomyosin contraction at the trailing edge of migrating DCs. Our findings not only demonstrate that semaphorin signals are involved in DC trafficking but also identify a previously unknown mechanism that induces actomyosin contraction as these cells pass through narrow gaps.
白细胞的再循环对于适当的免疫反应至关重要。然而，调节白细胞进入淋巴管的分子机制仍不清楚。在这里，我们表明，丛生蛋白 A1 是 III 类和 VI 类 semaphorin 的主要受体成分，对于树突状细胞 (DC) 进入淋巴管至关重要。此外，我们表明，semaphorin Sema3A 而不是 Sema6C 或 Sema6D 是 DC 迁移所必需的，并且淋巴管产生的 Sema3A 促进了迁移的 DC 后缘处的肌动球蛋白收缩。我们的发现不仅表明 semaphorin 信号参与了 DC 迁移，而且还确定了一种以前未知的机制，该机制在这些细胞通过狭窄的间隙时诱导肌动球蛋白收缩。
