Cytokine-Based Generation of CD49a(+)Eomes(-/+) Natural Killer Cell Subsets.
Cytokine-Based Generation of CD49a(+)Eomes(-/+) Natural Killer Cell Subsets.
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DOI：
10.3389/fimmu.2018.02126
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发表时间：
2018
影响因子：
7.3
通讯作者：
Wei H
中科院分区：
文献类型：
--
作者：
Ni X;Fu B;Zhang J;Sun R;Tian Z;Wei H
最近的研究已经在小鼠的不同器官中鉴定了CD 49 a +Eomes−和CD 49 a +Eomes+组织驻留NK（trNK）细胞亚群。然而，CD 49 a +Eomes-/+ NK细胞发育的特征和NK细胞中Eomes表达的调控仍不清楚。在这里，我们建立了一个体外的基于精氨酸的无饲养层系统，其中骨髓祖细胞分化为CD 49 a + NK细胞。IL-15被鉴定为该系统中支持CD 49 a + NK细胞的发育和维持的关键细胞因子。产生的CD 49 a + NK细胞是Eomes− CD 49 b −，与肝trNK细胞具有相同的表型。IL-4诱导产生的NK细胞中Eomes的表达，并将其转化为CD 49 a +Eomes+细胞，其在表型和功能上与子宫trNK细胞相似。此外，IL-4/STAT 6轴被鉴定为在CD 49 a +Eomes+诱导的NK细胞的产生中是重要的。总的来说，这些研究描述了一种产生CD 49 a +Eomes-/+ NK细胞亚群的方法，并证明了IL-15和IL-4在这些细胞的分化中的重要作用。这些发现有可能为发展研究奠定基础的NK细胞的不同亚群的产生和过继NK细胞转移疗法的应用。
Recent studies have identified CD49a+Eomes− and CD49a+Eomes+ subsets of tissue-resident NK (trNK) cells in different organs of the mouse. However, the characteristics of CD49a+Eomes−/+ NK cell development and the regulation of Eomes expression in NK cells remain unclear. Here, we established an in vitro cytokine-based feeder-free system in which bone marrow progenitor cells differentiate into CD49a+ NK cells. IL-15 was identified as being the key cytokine in this system that supported the development and maintenance of CD49a+ NK cells. The CD49a+ NK cells generated were Eomes−CD49b− and shared the same phenotype as hepatic trNK cells. IL-4 induced the expression of Eomes in generated NK cells and converted them into CD49a+Eomes+ cells, which were phenotypically and functionally similar to uterine trNK cells. Moreover, the IL-4/STAT6 axis was identified as being important in the generation of CD49a+Eomes+ induced NK cells. Collectively, these studies describe an approach to generate CD49a+Eomes−/+ subsets of NK cells and demonstrate important roles for IL-15 and IL-4 in the differentiation of these cells. These findings have potential for developmental research underlying the generation of different subsets of NK cells and the application of adoptive NK cell transfer therapies.
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DOI：
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