昂热大学Christelle Harly研究小组提出了转录因子NFIL3驱动先天淋巴样细胞从淋巴样祖细胞分化。相关论文于2025年10月30日发表在《免疫学》杂志上。

使用Il7r谱系追踪motheme菌株，该研究组在motheme骨髓（BM）中鉴定了淋巴样祖细胞和Tcf7⁺ ILC祖细胞之间的发育中间体。这些中间产物的转录分析确定了转录因子核因子，白细胞介素3调节（NFIL3）的早期表达。NFIL3^−/−小鼠缺乏所有BM ILC指定的前体。NFIL3在淋巴样祖细胞中的强制表达诱导Tcf7⁺ ILC谱系细胞能够产生所有ILC亚群和传统的自然杀伤细胞。淋巴样前体中NFIL3的短暂活性重现了BM ILC的体外发育，导致所有成年ILC的产生。从机制上讲，NFIL3通过诱导ILC发育的关键转录调控因子——tox、Id2、Gata3、Tcf7和Zbtb16的表达，启动ILC规范。他们的研究结果表明，NFIL3在ILC规范中发挥着重要作用，并为产生具有潜在治疗效用的ILC谱系细胞提供了一种体外方法。

据介绍，了解先天淋巴样细胞（ILC）特异性的启动机制可以揭示ILC在免疫和组织稳态中的功能是如何被编程的。

附：英文原文

Title: The transcription factor NFIL3 drives innate lymphoid cell specification from lymphoid progenitors

Author: Joseph Léger, Eva Artano, Delphine Coulais, Naomie Belletoise, Raoudha Fadhloun, Devin Kenney, Avinash Bhandoola, Christelle Harly

Issue&Volume: 2025-10-30

Abstract: Understanding the mechanisms that initiate innate lymphoid cell (ILC) specification may reveal how ILC functions in immunity and tissue homeostasis are programmed. Using an Il7r-lineage tracing mouse strain, we identified developmental intermediates between lymphoid progenitors and Tcf7+ ILC progenitors in the mouse bone marrow (BM). Transcriptional analysis of these intermediates identified very early expression of the transcription factor nuclear factor, interleukin 3 regulated (NFIL3). Nfil3/ mice lacked all BM ILC-specified precursors. Forced expression of NFIL3 in lymphoid progenitors induced Tcf7+ ILC-lineage cells capable of generating all ILC subsets and conventional natural killer cells. Transient activity of NFIL3 in lymphoid precursors recapitulated BM ILC development in vitro, leading to the generation of all adult ILCs. Mechanistically, NFIL3 initiated ILC specification by inducing expression of key transcriptional regulators of ILC development—Tox, Id2, Gata3, Tcf7, and Zbtb16. Our findings indicate an apex role for NFIL3 in ILC specification and provide an in vitro approach to generate ILC-lineage cells with potential therapeutic utility.

DOI: 10.1016/j.immuni.2025.10.005

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00435-2