Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II

Publisher Website
Google Scholar
Abstract
Tissue-resident leukocytes migrate to draining lymph nodes after being activated. Kumanogoh and colleagues show that such entry requires semaphorin 3A, produced by lymphatic vessels, to activate plexin-A1 receptors on migrating dendritic cells. 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.