NK cell activation by dendritic cells (DCs) requires the formation of a synapse leading to IL-12 polarization in DCs.
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.
Borg
Christophe
C
Immunology Unit, ERM0208 Institut National de la Santé et de la Recherche Médicale, Department of Clinical Biology, Institut Gustave Roussy, 39 rue C. Desmoulins, 94805 Villejuif Cedex, France.
Jalil
Abdelali
A
Laderach
Diego
D
Maruyama
Kouji
K
Wakasugi
Hiro
H
Charrier
Sabine
S
Ryffel
Bernhard
B
Cambi
Alessandra
A
Figdor
Carl
C
Vainchenker
William
W
Galy
Anne
A
Caignard
Anne
A
Zitvogel
Laurence
L
D000818:Animals; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D016764:Cell Polarity / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D013569:Synapses / Q000276:immunology*
D015815:Cell Adhesion Molecules; D018664:Interleukin-12; D007371:Interferon-gamma