NK cell activation by dendritic cells (DCs) requires the formation of a synapse leading to IL-12 polarization in DCs

Blood. 2004 Nov 15;104(10):3267-75. doi: 10.1182/blood-2004-01-0380. Epub 2004 Jul 8.


Mature dendritic cells (mDCs) can trigger the effector functions of natural killer (NK) cells. Knock-out, small-interfering RNA or neutralizing antibodies targeting interleukin 12 (IL-12) subunits revealed a critical role for IL-12 in NK cell interferon gamma (IFN-gamma) secretion promoted by mDCs. However, NK cell activation by DCs also required direct cell-to-cell contacts. DC-mediated NK cell activation involved the formation of stimulatory synapses between DCs and NK cells. The formation of DC/NK cell conjugates depended on cytoskeleton remodeling and lipid raft mobilization in DCs. Moreover, the disruption of the DC cytoskeleton using pharmacologic agents or the loss-of-function mutation of the Wiskott-Aldrich syndrome protein abolished the DC-mediated NK cell activation. Synapse formation promoted the polarized secretion of preassembled stores of IL-12 by DCs toward the NK cell. The synaptic delivery of IL-12 by DCs was required for IFN-gamma secretion by NK cells, as assessed using inhibitors of cytoskeleton rearrangements and transwell experiments. Therefore, the cross-talk between DCs and NK cells is dictated by functional synapses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules / metabolism
  • Cell Communication / immunology*
  • Cell Polarity / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism*
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Mice
  • Mice, Inbred Strains
  • Mice, Mutant Strains
  • Synapses / immunology*


  • Cell Adhesion Molecules
  • Interleukin-12
  • Interferon-gamma