Dendritic cell and natural killer cell cross-talk: a pivotal role of CX3CL1 in NK cytoskeleton organization and activation
Dendritic cell and natural killer cell cross-talk: a pivotal role of CX3CL1 in NK cytoskeleton organization and activation
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DOI：
10.1182/blood-2007-12-126888
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发表时间：
2008-12-01
期刊：
影响因子：
20.3
通讯作者：
Borg, Christophe
中科院分区：
文献类型：
--
作者：
Pallandre, Jean R.;Krzewski, Konrad;Borg, Christophe
导致自然杀伤淋巴细胞（NK）和树突状细胞（DC）相互作用的初始分子事件在很大程度上是未知的。本文研究了成熟树突状细胞（mDCs）上表达的趋化因子CX3CL1 （fractalkine）的作用。我们发现CX3CL1促进NK被mdc激活。抗体阻断CX3CL1后，未发生活化，但主要组织相容性复合体（MHC） I类中和恢复了dc介导的NK活化，提示CX3CL1信号传导与抑制性KIR功能之间存在相互作用。然后使用引入抑制受体KIR2DL1的YTS NK细胞系。当CX3CL1功能正常时，KIR2DL1的存在并未降低HLA-Cw4 DC对YTS的激活。相比之下，CX3CL1中和导致HLA-Cw4 mDCs培养的YTSKIR2DL1中杀伤细胞免疫球蛋白样受体（KIR）磷酸化和SHP-1募集。此外，CX3CL1中和促进了YTS NK细胞中脂筏的分散和细胞骨架重排所需的多蛋白复合物的形成。这些发现表明CX3CL1在成熟dc激活静息NK细胞中的关键作用。(血。2008;112:4420 - 4424)
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 YTSKIR2DL1 cultured with HLA-Cw4 mDCs. Moreover, CX3CL1 neutralization promoted dispersion of lipid rafts and the formation of a multiprotein complex required for cytoskeletal re-arrangements in YTS NK cells. These findings point to a pivotal role of CX3CL1 in the activation of resting NK cells by mature DCs. (Blood. 2008;112:4420-4424)