NK cell activation by dendritic cells (DCs) requires the formation of a synapse leading to IL-12 polarization in DCs
NK cell activation by dendritic cells (DCs) requires the formation of a synapse leading to IL-12 polarization in DCs
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DOI：
10.1182/blood-2004-01-0380
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发表时间：
2004-11-15
期刊：
影响因子：
20.3
通讯作者：
Zitvogel, L
中科院分区：
文献类型：
--
作者：
Borg, C;Jalil, A;Zitvogel, L
成熟树突状细胞（mDC）可以触发自然杀伤（NK）细胞的效应子功能。靶向白细胞介素12（IL-12）亚基的敲除、小干扰RNA或中和抗体揭示了IL-12在mDC促进的NK细胞干扰素γ（IFN-γ）分泌中的关键作用。然而，通过DC的NK细胞活化也需要直接的细胞-细胞接触。DC介导的NK细胞活化涉及DC和NK细胞之间刺激性突触的形成。DC/NK细胞结合物的形成依赖于DC的细胞骨架重塑和脂筏动员。此外，使用药理学试剂或Wiskott-Aldrich综合征蛋白的功能丧失突变破坏DC细胞骨架废除了DC介导的NK细胞活化。突触的形成促进了DC向NK细胞的IL-12的预组装储存的极化分泌。如使用细胞骨架重排抑制剂和transwell实验所评估的，NK细胞分泌IFN-γ需要DC的IL-12的突触递送。因此，DC和NK细胞之间的串扰由功能性突触决定。(C)2004年，美国血液学会。
Mature dendritic cells (mDCs) can trigger the effector functions of natural killer (NK) cells. Knock-out, small-interfering RNA or neutralizing antibodies targeting interleukin 12 (IL-12) subunits revealed a critical role for IL-12 in NK cell interferon gamma (IFN-gamma) secretion promoted by mDCs. However, NK cell activation by DCs also required direct cell-to-cell contacts. DC-mediated NK cell activation involved the formation of stimulatory synapses be-tween DCs and NK cells. The formation of DC/NK cell conjugates depended on cytoskeleton remodeling and lipid raft mobilization in DCs. Moreover, the disruption of the DC cytoskeleton using pharmacologic agents or the loss-of-function mutation of the Wiskott-Aldrich syndrome protein abolished the DC-mediated NK cell activation. Synapse formation promoted the polarized secretion of preassembled stores of IL-12 by DCs toward the NK cell. The synaptic delivery of IL-12 by DCs was required for IFN-gamma secretion by NK cells, as assessed using inhibitors of cytoskeleton rearrangements and transwell experiments. Therefore, the cross-talk between DCs and NK cells is dictated by functional synapses. (C) 2004 by The American Society of Hematology.