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Publication : Cytokine-Based Generation of CD49a<sup>+</sup>Eomes<sup>-/+</sup> Natural Killer Cell Subsets.

First Author  Ni X Year  2018
Journal  Front Immunol Volume  9
Pages  2126 PubMed ID  30319610
Mgi Jnum  J:295472 Mgi Id  MGI:6460597
Doi  10.3389/fimmu.2018.02126 Citation  Ni X, et al. (2018) Cytokine-Based Generation of CD49a(+)Eomes(-/+) Natural Killer Cell Subsets. Front Immunol 9:2126
abstractText  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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