文章：

细胞因子增强NK细胞外泌体的细胞溶解活性

Cytokine-enhanced cytolytic activity of exosomes from NK Cells 

原文发布日期：2021-07-27 

英文摘要：

Natural killer (NK) cells play key roles in immune surveillance against tumors and viral infection. NK cells distinguish abnormal cells from healthy cells by cell–cell interaction with cell surface proteins and then attack target cells via multiple mechanisms. In addition, extracellular vesicles (EVs) derived from NK cells (NK-EVs), including exosomes, possess cytotoxic capacity against tumor cells, but their characteristics and regulation by cytokines remain unknown. Here, we report that EVs derived from human NK-92 cells stimulated with IL-15 + IL-21 show enhanced cytotoxic capacity against tumor cells. Major cytolytic granules, granzyme B and granzyme H, are enriched by IL-15 + IL-21 stimulation in NK-EVs; however, knockout experiments reveal those cytolytic granules are independent of enhanced cytotoxic capacity. To find out the key molecules, mass spectrometry analyses were performed with different cytokine conditions, no cytokine, IL-15, IL-21, or IL-15 + IL-21. We then found that CD226 (DNAM-1) on NK-EVs is enriched by IL-15 + IL-21 stimulation and that blocking antibodies against CD226 reduced the cytolytic activity of NK-EVs. We also show NK-EVs are taken up by target cells via macropinocytosis. Collectively, our findings elucidate the novel properties of NK-EVs and the mechanism of their incorporation into target cells. 

摘要翻译： 

自然杀伤细胞（NK细胞）在针对肿瘤和病毒感染的免疫监视中起关键作用。NK细胞通过细胞表面蛋白的细胞间相互作用区分异常细胞与健康细胞，并通过多种机制攻击靶细胞。此外，源自NK细胞的细胞外囊泡（NK-EVs）（包括外泌体）对肿瘤细胞具有细胞毒性能力，但其特性及细胞因子的调控机制尚不明确。本研究报道，经IL-15与IL-21联合刺激的人NK-92细胞源EVs对肿瘤细胞展现出增强的细胞毒性能力。主要细胞溶解颗粒——颗粒酶B和颗粒酶H在IL-15+IL-21刺激下于NK-EVs中富集，但基因敲除实验表明这些细胞溶解颗粒与增强的细胞毒性能力无关。通过质谱分析比较不同细胞因子条件（无细胞因子、IL-15、IL-21或IL-15+IL-21联合刺激），发现IL-15+IL-21刺激能富集NK-EVs上的CD226（DNAM-1）分子，且抗CD226阻断抗体会降低NK-EVs的细胞溶解活性。研究同时证实NK-EVs通过巨胞饮作用被靶细胞摄取。综上，本研究阐明了NK-EVs的新特性及其被靶细胞摄入的作用机制。

原文链接：

Cytokine-enhanced cytolytic activity of exosomes from NK Cells