Regulatory role of NKp44, NKp46, DNAM-1 and NKG2D receptors in the interaction between NK cells and trophoblast cells. Evidence for divergent functional profiles of decidual versus peripheral NK cells

Regulatory role of NKp44, NKp46, DNAM-1 and NKG2D receptors in the interaction between NK cells and trophoblast cells. Evidence for divergent functional profiles of decidual versus peripheral NK cells
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DOI:
10.1093/intimm/dxn105
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发表时间:
2008-11-01
影响因子:
4.4
通讯作者:
Mingari, Maria Cristina
Mingari, Maria Cristina
中科院分区:
医学3区
文献类型:
--
作者:
Vacca, Paola;Cantoni, Claudia;Mingari, Maria Cristina

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在妊娠的前三个月期间,NK细胞占存在于人蜕膜中的淋巴样细胞的> 50%,在那里它们与滋养层细胞紧密接触。由于在蜕膜组织中,NK细胞的活化和功能可能是由这种相互作用引起的,因此我们分析了通过活化滋养层细胞上表达的NK受体识别的细胞配体。我们表明,这些细胞主要表达NKp 44和DNAM-1配体,这些配体和它们相应的受体之间的相互作用导致NK细胞触发。虽然活化的外周血NK(pNK)细胞溶解滋养层细胞系NK和JEG 3,但蜕膜NK(dNK)细胞不溶解。另一方面,它们释放VEGF、SDF-1、IP 10和大量IL-8。利用与K562靶细胞的相互作用来诱导最佳NK细胞触发,从而允许对dNK细胞引起的细胞溶解活性和细胞因子产生进行平行定量评估。虽然dNK细胞即使在高效应子:靶(E:T)比率下也不能杀死K562,但它们也在低E:T比率下释放大量IL-8,这与蜕膜组织内发生的dNK滋养层细胞相互作用相容。
During the first trimester of pregnancy NK cells represent > 50% of the lymphoid cells present in the human decidua where they reside in close contact with trophoblast cells. Because in decidual tissues NK cell activation and function may be induced by this interaction, we analyzed the cellular ligands recognized by activating NK receptors expressed on trophoblast cells. We show that these cells primarily express the NKp44 and DNAM-1 ligands and that interaction between these ligands and their corresponding receptors results in NK cell triggering. While activated peripheral blood NK (pNK) cells lysed the trophoblast cell lines JAR and JEG3, decidual NK (dNK) cells did not. On the other hand, they released VEGF, SDF-1, IP10 and large amounts of IL-8. Interaction with K562 target cells was exploited to induce optimal NK cell triggering, allowing a parallel, quantitative assessment of both cytolytic activity and cytokine production elicited by dNK cells. While dNK cells were unable to kill K562 even at high effector:target (E:T) ratios, they released large amounts of IL-8 also at low E:T ratios, a scenario compatible with dNK trophoblast cells interaction occurring within decidual tissues.