Pallandre, J. R. et al. Dendritic cell and natural killer cell cross-talk: a pivotal role of CX3CL1 in NK cytoskeleton organization and activation. Blood 112, 4420-4424

Inserm U645, EFS Bourgogne Franche Comté, University of Franche-Comté, IFR133, Besançon, France.
Blood (Impact Factor: 10.45). 09/2008; 112(12):4420-4. DOI: 10.1182/blood-2007-12-126888
Source: PubMed


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.

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    • "In general, the formation of stimulatory synapses between DCs and NK cells plays a critical role during NK cell activation induced by DC-derived cytokines, including IL-12 (47). Also, the interaction of CXC3CL1 expressed on DCs with CX3CR1 on NK cells results in IFN-γ release by NK cells (48) and it has been shown that influenza virus-infected DCs can support IFN-γ production by triggering the activating receptors NKp46 and NKG2D (49). "
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    • "DCs and NK cells specialize in complementary functions, including IL-12 or IFN-α/β secretion and antigen presentation for the former, and IFN-γ secretion and killing of infected or tumor cells for the latter . Thus, the outcome of NK-DC crosstalk is likely to increase lytic activity against malignancies compared to NK cell cytotoxicity alone (Walzer et al., 2005; Pallandre et al., 2008; Wehner et al., 2009; Jacobs and Ullrich, 2012). Additional investigations are "
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