Dendritic cell and natural killer cell cross-talk: a pivotal role of CX3CL1 in NK cytoskeleton organization and activation.
Initial molecular events leading to natural killer lymphocyte (NK) and dendritic cell (DC) interactions are largely unknown. Here, the role of CX3CL1 (fractalkine), a chemokine expressed on mature dendritic cells (mDCs) has been investigated. We show that CX3CL1 promotes NK activation by mDCs. After blocking of CX3CL1 by antibody, no activation occurred but major histocompatibility complex (MHC) class I neutralization restored DC-mediated NK activation, suggesting an interaction between CX3CL1 signaling and the functioning of inhibitory KIR. Then the YTS NK cell line, in which the inhibitory receptor KIR2DL1 had been introduced, was used. The presence of KIR2DL1 did not decrease YTS activation by HLA-Cw4 DC when CX3CL1 was functional. In contrast, CX3CL1 neutralization led to killer cell immunoglobulin-like receptor (KIR) phosphorylation and SHP-1 recruitment in YTS(KIR2DL1) cultured with HLA-Cw4 mDCs. Moreover, CX3CL1 neutralization promoted dispersion of lipid rafts and the formation of a multiprotein complex required for cytoskeletal rearrangements in YTS NK cells. These findings point to a pivotal role of CX3CL1 in the activation of resting NK cells by mature DCs.
Pallandre
Jean R
JR
Inserm U645, EFS Bourgogne Franche Comté, University of Franche-Comté, IFR133, Besançon, France.
Krzewski
Konrad
K
Bedel
Romain
R
Ryffel
Bernhard
B
Caignard
Anne
A
Rohrlich
Pierre Simon
PS
Pivot
Xavier
X
Tiberghien
Pierre
P
Zitvogel
Laurence
L
Strominger
Jack L
JL
Borg
Christophe
C
D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D002450:Cell Communication / Q000276:immunology / Q000502:physiology; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism*; D003713:Dendritic Cells / Q000502:physiology*; D019281:Dimerization; D006801:Humans; D054992:Immunological Synapses / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D007694:Killer Cells, Natural / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020239:Receptor Cross-Talk / Q000276:immunology*; D019707:Receptors, Chemokine / Q000235:genetics; D054340:Receptors, KIR / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology
D000073883:CX3C Chemokine Receptor 1; D054360:Chemokine CXCL1; C471885:Cx3cr1 protein, mouse; D019707:Receptors, Chemokine; D054340:Receptors, KIR