Innate lymphoid cell development requires TOX-dependent generation of a common ILC progenitor

Subtypes of innate lymphoid cells (ILC), defined by effector function and transcription factor expression, have recently been identified. In the adult, ILC derive from common lymphoid progenitors in bone marrow, although transcriptional regulation of the developmental pathways involved remains poorly defined. TOX is required for development of lymphoid tissue inducer cells, a type of ILC3 required for lymph node organogenesis, and NK cells, a type of ILC1. We show here that production of multiple ILC lineages requires TOX, as a result of TOX-dependent development of common ILC progenitors. Comparative transcriptome analysis demonstrated failure to induce various aspects of the ILC gene program in the absence of TOX, implicating this nuclear factor as a key early determinant of ILC lineage specification. TOX KO vs. wild tyype近期研究依据效应功能与转录因子表达特征，鉴定出了固有淋巴样细胞（innate lymphoid cells, ILC）的多个亚型。成体体内的ILC源自骨髓内的常见淋巴祖细胞，但其相关发育通路的转录调控机制仍未得到充分阐明。TOX对于淋巴组织诱导细胞——一类参与淋巴结器官发生的ILC3亚型——以及自然杀伤细胞（natural killer cells, NK，属于ILC1亚型）的发育不可或缺。本研究证实，多种ILC谱系的生成均依赖TOX，这一作用源于TOX介导的常见ILC祖细胞发育过程。比较转录组分析结果显示，在缺失TOX的情况下，ILC基因程序的诸多环节无法正常激活，表明该核因子是ILC谱系特化的关键早期决定因子。本研究设置了TOX基因敲除（knockout, KO）与野生型（wild type, WT）两组对照