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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actomyosin / metabolism
  • Adoptive Transfer
  • Animals
  • Cell Migration Assays, Leukocyte
  • Cell Movement / immunology
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Dendritic Cells / pathology
  • Gene Knock-In Techniques
  • Immunity
  • Lymphatic Vessels / metabolism*
  • Lymphatic Vessels / pathology
  • Mice
  • Mice, Knockout
  • Muscle Contraction
  • Myosin Type II / immunology
  • Myosin Type II / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / immunology
  • Nerve Tissue Proteins / metabolism*
  • Neuropilin-1 / genetics
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism*
  • Semaphorins / genetics
  • Semaphorins / immunology
  • Semaphorins / metabolism*
  • Signal Transduction


  • Nerve Tissue Proteins
  • Plxna1 protein, mouse
  • Receptors, Cell Surface
  • Semaphorins
  • Neuropilin-1
  • Actomyosin
  • Myosin Type II