PLZF expression maps the early stages of ILC1 lineage development
PLZF expression maps the early stages of ILC1 lineage development
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DOI：
10.1073/pnas.1423244112
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发表时间：
2015-04-21
影响因子：
11.1
通讯作者：
Bendelac, Albert
中科院分区：
文献类型：
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作者：
Constantinides, Michael G.;Gudjonson, Herman;Bendelac, Albert
在最近区别于循环的经典NK(CNK)细胞的各种组织驻留的NK样细胞中，肝脏固有淋巴样细胞(ILC)1型(ILC1s)被证明是一种独特的谱系，起源于一种新的表达早幼粒细胞白血病锌指(PLZF)的ILC前体(ILCP)，严格致力于ILC1、ILC2和ILC3谱系。在这里，我们使用PLZF报告小鼠和细胞转移分析，研究了ILC1s的发育过程，并证明了与先前归因于CNK谱系的阶段有很大重叠，包括前NK前、前NK前体(Pre-NKP)、精制NKP(RNKP)和未成熟NK(Ink)。尽管它们起源于不同的前体，但ILC1和CNK谱系在早期遵循平行发展，在墨迹阶段后期分化，在个体发育早期ILC1s明显优于CNKs。虽然有一组ILC1基因的表达依赖于PLZF，典型的包括IL7r，但这些基因中的大多数也在ILC1s和CNKS之间存在差异表达，这表明PLZF与其他尚未确定的因素一起导致了这些谱系之间的差异。
Among the variety of tissue-resident NK-like populations recently distinguished from recirculating classical NK (cNK) cells, liver innate lymphoid cells (ILC) type 1 (ILC1s) have been shown to represent a distinct lineage that originates from a novel promyelocytic leukaemia zinc finger (PLZF)-expressing ILC precursor (ILCP) strictly committed to the ILC1, ILC2, and ILC3 lineages. Here, using PLZF-reporter mice and cell transfer assays, we studied the developmental progression of ILC1s and demonstrated substantial overlap with stages previously ascribed to the cNK lineage, including pre-pro-NK, pre-NK precursor (pre-NKP), refined NKP (rNKP), and immature NK (iNK). Although they originated from different precursors, the ILC1 and cNK lineages followed a parallel progression at early stages and diverged later at the iNK stage, with a striking predominance of ILC1s over cNKs early in ontogeny. Although a limited set of ILC1 genes depended on PLZF for expression, characteristically including Il7r, most of these genes were also differentially expressed between ILC1s and cNKs, indicating that PLZF together with other, yet to be defined, factors contribute to the divergence between these lineages.