Immune Surveillance Properties of Human NK Cell-Derived Exosomes
Immune Surveillance Properties of Human NK Cell-Derived Exosomes
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DOI：
10.4049/jimmunol.1101988
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发表时间：
2012-09-15
影响因子：
4.4
通讯作者：
Fais, Stefano
中科院分区：
文献类型：
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作者：
Lugini, Luana;Cecchetti, Serena;Fais, Stefano
外泌体是由正常和肿瘤细胞释放的纳米囊泡，其在细胞培养上清液和人类生物流体（例如血浆）中是可检测的。由“正常”细胞释放的外泌体的功能还不清楚。事实上，已经对来自造血细胞的外泌体进行了几项研究，但对NK细胞外泌体知之甚少，尽管这些细胞在先天性和适应性免疫中很重要。在这篇论文中，我们报道了从健康供体的血液中新鲜分离的静息和活化的NK细胞释放表达NK细胞的典型蛋白质标志物并含有杀伤蛋白（即，Fas配体和穿孔素分子）。这些纳米囊泡显示出对几种肿瘤细胞系和活化的免疫细胞的细胞毒性活性，但不静息免疫细胞。我们还表明，NK衍生的外泌体被肿瘤靶细胞摄取，但不被静息PBMC摄取。从健康供体的血浆中纯化的外泌体表达NK细胞标志物，包括CD 56（+）和穿孔素，并对不同的人肿瘤靶细胞和活化的免疫细胞发挥细胞毒性活性。这项研究的结果提出了NK细胞来源的外泌体在免疫监视和稳态中的重要作用。此外，这项研究支持使用外泌体作为仿生纳米囊泡的一个几乎完美的例子，可能用于未来针对各种疾病（包括肿瘤）的治疗方法。免疫学杂志，2012，189：2833-2842。
Exosomes are nanovesicles released by normal and tumor cells, which are detectable in cell culture supernatant and human biological fluids, such as plasma. Functions of exosomes released by "normal" cells are not well understood. In fact, several studies have been carried out on exosomes derived from hematopoietic cells, but very little is known about NK cell exosomes, despite the importance of these cells in innate and adaptive immunity. In this paper, we report that resting and activated NK cells, freshly isolated from blood of healthy donors, release exosomes expressing typical protein markers of NK cells and containing killer proteins (i.e., Fas ligand and perforin molecules). These nanovesicles display cytotoxic activity against several tumor cell lines and activated, but not resting, immune cells. We also show that NK-derived exosomes undergo uptake by tumor target cells but not by resting PBMC. Exosomes purified from plasma of healthy donors express NK cell markers, including CD56(+) and perforin, and exert cytotoxic activity against different human tumor target cells and activated immune cells as well. The results of this study propose an important role of NK cell-derived exosomes in immune surveillance and homeostasis. Moreover, this study supports the use of exosomes as an almost perfect example of biomimetic nanovesicles possibly useful in future therapeutic approaches against various diseases, including tumors. The Journal of Immunology, 2012, 189: 2833-2842.