Eomesodermin and T-bet mark developmentally distinct human natural killer cells
Eomesodermin and T-bet mark developmentally distinct human natural killer cells
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DOI：
10.1172/jci.insight.90063
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发表时间：
2017-03-09
期刊：
影响因子：
8
通讯作者：
Reiner, Steven L.
中科院分区：
文献类型：
--
作者：
Collins, Amelie;Rothman, Nyanza;Reiner, Steven L.
人类胎儿和新生儿免疫系统的不成熟常常被用来解释他们对感染的易感性增加；然而，胎儿早期先天免疫系统的发育仍未得到完全探索。我们现在表明，在成人（或出生后）人体循环中发现的最成熟的 NK 细胞 (CD94(-)CD16(+)) 在个体发育过程中不存在。研究发现，人类胎儿 NK 细胞表达 2 种特征性 T 盒转录因子，即脱中胚层蛋白 (Eomes) 和 T-bet，这两种因子对于所有小鼠 NK 和 NK 样细胞的发育至关重要。然而，个体发育过程中 Eomes 和 T-bet 表达的单细胞模式揭示了一种相互优势的刻板模式，未成熟的 NK 细胞表达更高量的 Eomes，而更成熟的 NK 细胞则以更丰富的 T-bet 为标志。我们还观察到人类个体发育过程中组织特异性 NK 细胞成熟的刻板模式，胎儿肝脏比胎儿骨髓、脾脏或肺对 NK 细胞成熟的限制更大。这些结果支持了这样的假设：人类 NK 细胞的成熟在出生后一直受到离散限制，并提供了一个框架来更好地了解胎儿和新生儿对感染的易感性增加。
Immaturity of the immune system of human fetuses and neonates is often invoked to explain their increased susceptibility to infection; however, the development of the fetal innate immune system in early life remains incompletely explored. We now show that the most mature NK cells found in adult (or postnatal) human circulation (CD94(-)CD16(+)) are absent during ontogeny. Human fetal NK cells were found to express the 2 signature T-box transcription factors essential for the development of all murine NK and NK-like cells, eomesodermin (Eomes) and T-bet. The single-cell pattern of Eomes and T-bet expression during ontogeny, however, revealed a stereotyped pattern of reciprocal dominance, with immature NK cells expressing higher amounts of Eomes and more mature NK cells marked by greater abundance of T-bet. We also observed a stereotyped pattern of tissue-specific NK cell maturation during human ontogeny, with fetal liver being more restrictive to NK cell maturity than fetal bone barrow, spleen, or lung. These results support the hypothesis that maturation of human NK cells has a discrete restriction until postnatal life, and provide a framework to better understand the increased susceptibility of fetuses and newborns to infection.