Laboratory of Molecular Oncology, Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec, Canada.
Department of Medicine, University of Montréal, Montréal, Québec, Canada.
Nat Immunol. 2016 Apr;17(4):387-96. doi: 10.1038/ni.3369. Epub 2016 Feb 15.
Activation of natural killer (NK) cells by hematopoietic target cells is controlled by the SLAM family of receptors and by the associated SAP family of adaptors. Here we found that SLAM receptors also enhanced NK cell activation by nonhematopoietic target cells, which lack ligands for SLAM receptors. This function was mediated by SLAMF6, a homotypic SLAM receptor found on NK cells and other hematopoietic cells, and was regulated by SAP adaptors, which uncoupled SLAM receptors from phosphatase SHP-1 and diminished the effect of SLAMF6 on NK cell responsiveness toward nonhematopoietic cells. Thus, in addition to their role in NK cell activation by hematopoietic cells, the SLAM-SAP pathways influence responsiveness toward nonhematopoietic targets by a process akin to NK cell 'education'.
自然杀伤 (NK) 细胞被造血靶细胞激活受到 SLAM 家族受体和相关 SAP 家族衔接蛋白的调控。在这里，我们发现 SLAM 受体还增强了非造血靶细胞对 NK 细胞的激活作用，而这些非造血靶细胞缺乏 SLAM 受体的配体。这种功能是由 NK 细胞和其他造血细胞上发现的同种型 SLAM 受体 SLAMF6 介导的，由 SAP 衔接蛋白调节，SAP 衔接蛋白将 SLAM 受体与磷酸酶 SHP-1 解偶联，并减弱 SLAMF6 对 NK 细胞对非造血细胞反应性的影响。因此，除了在造血细胞激活 NK 细胞中的作用外，SLAM-SAP 途径还通过类似于 NK 细胞“教育”的过程影响对非造血靶标的反应性。
