Mutual activation of natural killer cells and monocytes mediated by NKp80-AICL interaction
Mutual activation of natural killer cells and monocytes mediated by NKp80-AICL interaction
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DOI：
10.1038/ni1402
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发表时间：
2006-12-01
影响因子：
30.5
通讯作者：
Steinle, Alexander
中科院分区：
文献类型：
--
作者：
Welte, Stefan;Kuttruff, Sabrina;Steinle, Alexander
由自然杀伤 (NK) 细胞基因复合体（例如 NKG2D）编码的受体控制 NK 细胞的反应性。然而，NK 细胞基因复合体编码的人 NK 细胞受体 NKp80 的功能和配体仍然难以捉摸。在这里，我们证明 NKp80 与基因相关的“孤儿”受体 AICL 结合，与 NKp80 一样，啮齿类动物中不存在这种受体。我们将 AICL 定义为一种骨髓特异性激活受体，可通过 Toll 样受体刺激上调。 AICL-NKp80 相互作用促进 NK 细胞介导的恶性骨髓细胞的细胞溶解。此外，在 NK 细胞和单核细胞之间的相互作用过程中，NKp80 刺激两种细胞类型释放促炎细胞因子。因此，通过特异性桥接 NK 细胞和骨髓细胞，NKp80-AICL 相互作用可能有助于炎症部位免疫反应的启动和维持。
Receptors encoded by the natural killer (NK) cell gene complex (such as NKG2D) govern the reactivity of NK cells. However, the function and ligand(s) of the NK cell gene complex-encoded human NK cell receptor NKp80 remain elusive. Here we demonstrate that NKp80 binds to the genetically linked 'orphan' receptor AICL, which, like NKp80, is absent from rodents. We defined AICL as a myeloid-specific activating receptor that is upregulated by Toll-like receptor stimulation. AICL-NKp80 interactions promoted NK cell-mediated cytolysis of malignant myeloid cells. In addition, during crosstalk between NK cells and monocytes, NKp80 stimulated the release of proinflammatory cytokines from both cell types. Thus, by specifically bridging NK cells and myeloid cells, NKp80-AICL interactions may contribute to the initiation and maintenance of immune responses at sites of inflammation.