Dendritic cell and natural killer cell cross-talk: a pivotal role of CX3CL1 in NK cytoskeleton organization and activation.

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

Blood

journal_title

Blood

authors

Pallandre JR,Krzewski K,Bedel R,Ryffel B,Caignard A,Rohrlich PS,Pivot X,Tiberghien P,Zitvogel L,Strominger JL,Borg C

doi

10.1182/blood-2007-12-126888

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

4420-4

issue

12

eissn

0006-4971

issn

1528-0020

pii

blood-2007-12-126888

journal_volume

112

pub_type

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