Abstract:
: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.
journal_name
Bloodjournal_title
Bloodauthors
Pallandre JR,Krzewski K,Bedel R,Ryffel B,Caignard A,Rohrlich PS,Pivot X,Tiberghien P,Zitvogel L,Strominger JL,Borg Cdoi
10.1182/blood-2007-12-126888subject
Has Abstractpub_date
2008-12-01 00:00:00pages
4420-4issue
12eissn
0006-4971issn
1528-0020pii
blood-2007-12-126888journal_volume
112pub_type
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