Differential Requirement for Nfil3 during NK Cell Development
Differential Requirement for Nfil3 during NK Cell Development
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DOI：
10.4049/jimmunol.1302605
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发表时间：
2014-03-15
影响因子：
4.4
通讯作者：
Carotta, Sebastian
中科院分区：
文献类型：
--
作者：
Seillet, Cyril;Huntington, Nicholas D.;Carotta, Sebastian
NK细胞可以分为不同的亚群，定位于不同的器官，表现出不同的分泌细胞因子和介导细胞毒作用的能力。尽管这些特征反映了NK细胞的组织特异性特化，但人们对控制这些不同亚群发展的因素知之甚少。碱性亮氨酸拉链转录因子Nfil3(E4bp4)对骨髓源性NK细胞的发育至关重要，但目前尚不清楚Nfil3对所有NK细胞亚群是否同样重要，也不清楚它是如何诱导NK谱系承诺的。在这篇文章中，我们证明了Nfil3是形成表达eome的NK细胞所必需的，包括常规的骨髓和胸腺NK细胞，而TRAIL(+)eome(-)NK细胞是独立于Nfil3发展的。在骨髓源性NK细胞的发育过程中，Nfil3的缺失导致Eome的表达减少，反之，在Nfil3(-/-)祖细胞中恢复Eome的表达，挽救了NK细胞的发育和成熟。综上所述，这些发现表明，Nfil3通过诱导Eome表达来驱动成熟NK细胞的形成，并揭示了NK细胞亚群对Nfil3的不同需求。
NK cells can be grouped into distinct subsets that are localized to different organs and exhibit a different capacity to secrete cytokines and mediate cytotoxicity. Despite these hallmarks that reflect tissue-specific specialization in NK cells, little is known about the factors that control the development of these distinct subsets. The basic leucine zipper transcription factor Nfil3 (E4bp4) is essential for bone marrow-derived NK cell development, but it is not clear whether Nfil3 is equally important for all NK cell subsets or how it induces NK lineage commitment. In this article, we show that Nfil3 is required for the formation of Eomes-expressing NK cells, including conventional medullary and thymic NK cells, whereas TRAIL(+) Eomes(-) NK cells develop independently of Nfil3. Loss of Nfil3 during the development of bone marrow-derived NK cells resulted in reduced expression of Eomes and, conversely, restoration of Eomes expression in Nfil3(-/-) progenitors rescued NK cell development and maturation. Collectively, these findings demonstrate that Nfil3 drives the formation of mature NK cells by inducing Eomes expression and reveal the differential requirements of NK cell subsets for Nfil3.