当前位置: X-MOL 学术J. Exp. Med. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
NK cells switch from granzyme B to death receptor-mediated cytotoxicity during serial killing.
Journal of Experimental Medicine ( IF 12.6 ) Pub Date : 2019-07-03 , DOI: 10.1084/jem.20181454
Isabel Prager 1 , Clarissa Liesche 2 , Hanna van Ooijen 3 , Doris Urlaub 1 , Quentin Verron 3 , Niklas Sandström 3 , Frank Fasbender 1 , Maren Claus 1 , Roland Eils 2 , Joël Beaudouin 4 , Björn Önfelt 5, 6 , Carsten Watzl 7
Affiliation  

NK cells eliminate virus-infected and tumor cells by releasing cytotoxic granules containing granzyme B (GrzB) or by engaging death receptors that initiate caspase cascades. The orchestrated interplay between both cell death pathways remains poorly defined. Here we simultaneously measure the activities of GrzB and caspase-8 in tumor cells upon contact with human NK cells. We observed that NK cells switch from inducing a fast GrzB-mediated cell death in their first killing events to a slow death receptor-mediated killing during subsequent tumor cell encounters. Target cell contact reduced intracellular GrzB and perforin and increased surface-CD95L in NK cells over time, showing how the switch in cytotoxicity pathways is controlled. Without perforin, NK cells were unable to perform GrzB-mediated serial killing and only killed once via death receptors. In contrast, the absence of CD95 on tumor targets did not impair GrzB-mediated serial killing. This demonstrates that GrzB and death receptor-mediated cytotoxicity are differentially regulated during NK cell serial killing.

中文翻译:

在连续杀伤过程中,NK细胞从粒酶B转换为死亡受体介导的细胞毒性。

NK细胞通过释放含有颗粒酶B(GrzB)的细胞毒性颗粒或通过接合启动半胱天冬酶级联反应的死亡受体来消除病毒感染和肿瘤细胞。两种细胞死亡途径之间精心策划的相互作用仍然不清楚。在这里,我们与人NK细胞接触后,同时测量肿瘤细胞中GrzB和caspase-8的活性。我们观察到,NK细胞从在其最初的杀伤事件中诱导快速的GrzB介导的细胞死亡转变为在随后的肿瘤细胞遭遇期间的缓慢的死亡受体介导的杀伤。随着时间的推移,靶细胞接触减少了NK细胞中的细胞内GrzB和穿孔素,并增加了表面CD95L,显示了如何控制细胞毒性途径的转换。没有穿孔素 NK细胞无法执行GrzB介导的连续杀伤,只能通过死亡受体杀死一次。相反,肿瘤靶标上没有CD95不会损害GrzB介导的连续杀伤作用。这表明在NK细胞系列杀伤过程中,GrzB和死亡受体介导的细胞毒性被不同地调节。
更新日期:2019-09-03
down
wechat
bug