Essential role of the TNF-TNFR2 cognate interaction in mouse dendritic cell-natural killer cell crosstalk
Essential role of the TNF-TNFR2 cognate interaction in mouse dendritic cell-natural killer cell crosstalk
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DOI：
10.1182/blood-2006-06-026385
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发表时间：
2007-04-15
期刊：
影响因子：
20.3
通讯作者：
Vujanovic, Nikola L.
中科院分区：
文献类型：
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作者：
Xu, Jun;Chakrabarti, Ayan K.;Vujanovic, Nikola L.
树突状细胞（dc）和自然杀伤细胞（NK）是先天免疫系统的重要组成部分，在适应性免疫反应的启动和调节中起着核心作用。在早期的关键免疫活动中，dc和NK细胞通过细胞间接触相互作用并相互调节。dc - nk细胞串扰的分子介质在很大程度上是不确定的。在本研究中，我们在小鼠中发现DC刺激nk细胞分泌ifn - γ需要DC膜结合而不是分泌产物；通过增加DC跨膜肿瘤坏死因子（tmTNF）和nk细胞跨膜肿瘤坏死因子受体2 （tmTNFR2）的表达而增加；通过阻断TNF或TNFR2而非TNFR1抑制；通过敲除DC Tnf或nk细胞Tnfr2而不敲除DC Tnfr1或Tnfr2和nk细胞Tnf或Tnfr1而受损；并且在缺乏TNF的dc中通过重建tmTNF得以恢复，但不能被可溶性TNF模拟。我们还证明DC TNF和nk细胞TNFR2是DC介导的nk细胞增殖和细胞毒性活性扩增所必需的。这些新发现提供了DC- nk细胞串扰通过DC- tmTNF触发nk细胞tmTNFR2介导nk细胞功能增强的第一个证据。
Dendritic cells (DCs) and natural killer (NK) cells are essential components of the innate immune system and have a central role in initiation and regulation of adaptive immune responses. During the early critical immune activities, DCs and NK cells interact and reciprocally regulate each other via cell-cell contact. The molecular mediators of the DC-NK-cell crosstalk are largely undefined. In the present study, we show in mice that DC stimulation of NK-cell IFN-gamma secretion requires DC membranebound but not secreted products; is increased by augmenting the expression of DC transmembrane tumor necrosis factor (tmTNF) and NK-cell transmembrane TNF receptor type 2 (tmTNFR2); is inhibited by blocking TNF or TNFR2 but not TNFR1; is impaired by knocking out DC Tnf or NK-cell Tnfr2 but not DC Tnfr1 or Tnfr2 and NK-cell Tnf or Tnfr1; and is restored in TNF-deficient DCs by reconstituting tmTNF, but cannot be mimicked by soluble TNF. We also demonstrate that DC TNF and NK-cell TNFR2 are required for DC-mediated NK-cell proliferation and amplification of cytotoxic activity. These novel findings provide the first evidence that DC-NK-cell crosstalk mediates enhancement of NK-cell functions via triggering NK-cell tmTNFR2 by DC tmTNF.