Submitted December 3, 2007
Accepted April 1, 2008
Dendritic cell and natural killer cell cross-talk: a pivotal role of CX3CL1 in NK cytoskeleton organization and activation
Jean R. Pallandre, Konrad Krzewski, Romain Bedel, Bernhard Ryffel, Anne Caignard, Pierre Simon Rohrlich, Xavier Pivot, Pierre Tiberghien, Laurence Zitvogel, Jack L Strominger, and Christophe Borg*
INSERM U645, EFS Bourgogne Franche Comte, universite de Franche Comte, Besancon, France
Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
Immunology, GEM2358, CNRS, Orleans, France
Immunology, INSERM U753, Institut Gustave Roussy, Vuillejuif, France
Oncologie Médicale, CHU Jean Minjoz, Besancon, France
Immunology, INSERM U805, Institut Gustave Roussy, Vuillejuif, France
* Corresponding author; email: christophe.borg{at}efs.sante.fr.
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 (mDC) has been investigated. We show that CX3CL1 promotes NK activation by mDC. After blocking of CX3CL1 by antibody, no activation occurred but 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 KIR phosphorylation and SHP-1 recruitment in YTSKIR2DL1 cultured with HLA-Cw4 mDC. 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 by mature DC.
