Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II.
Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II.
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Recirculation of leukocytes is essential for proper immune responses. However, the molecular mechanisms that regulate leukocyte entry into the lymphatics remain unclear. Here we show that plexin-A1, a primary receptor component for class III and class VI semaphorins, is crucially involved in the entry of dendritic cells (DCs) into the lymphatics. Additionally, we show that Sema3A, but not Sema6C or Sema6D, is required for DC transmigration, and that Sema3A produced by the lymphatics promotes actomyosin contraction at the trailing edge of migrating DCs. These findings not only demonstrate that semaphorin-signals are involved in DC trafficking but also provide a novel mechanism that induces actomyosin contraction as these cells pass through narrow gaps.