Lautenberg Center for General and Tumor Immunology, Hebrew University Hadassah Medical School, Institute for Medical Research Israel-Canada, Jerusalem, Israel.
Blood. 2012 Nov 8;120(19):3915-24. doi: 10.1182/blood-2012-02-410795. Epub 2012 Sep 14.
Recent evidence suggests that kindlin-3 is a major coactivator, required for most, if not all, integrin activities. Here we studied the function of kindlin-3 in regulating NK cell activation by studying a patient with kindlin-3 deficiency (leukocyte adhesion deficiency-III). We found that kindlin-3 is required for NK cell migration and adhesion under shear force. Surprisingly, we also found that kindlin-3 lowers the threshold for NK cell activation. Loss of kindlin-3 has a pronounced effect on NK cell-mediated cytotoxicity triggered by single activating receptors. In contrast, for activation through multiple receptors, kindlin-3 deficiency is overcome and target cells killed. The realization that NK cell activity is impaired, but not absent in leukocyte adhesion deficiency, may lead to the development of more efficient therapy for this rare disease.
最近的证据表明，连接蛋白-3 是一种主要的共激活因子，对于大多数（如果不是全部）整合素活动都是必需的。在这里，我们通过研究一种连接蛋白-3 缺乏症（白细胞黏附缺陷 III 型）患者来研究连接蛋白-3 在调节 NK 细胞激活中的作用。我们发现连接蛋白-3 在剪切力下对 NK 细胞迁移和黏附是必需的。令人惊讶的是，我们还发现连接蛋白-3 降低了 NK 细胞激活的阈值。连接蛋白-3 的缺失对由单个激活受体触发的 NK 细胞介导的细胞毒性有显著影响。相比之下，对于通过多个受体的激活，连接蛋白-3 的缺乏被克服，靶细胞被杀死。认识到在白细胞黏附缺陷中，NK 细胞的活性受损但并未完全丧失，可能会为这种罕见疾病的治疗方法的发展带来新的契机。
