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 type根据效应功能与转录因子表达定义的固有淋巴样细胞（innate lymphoid cells, ILC）亚型近日已被成功鉴定。成年个体中的固有淋巴样细胞源自骨髓内的常见淋巴样祖细胞，但其相关发育通路的转录调控机制仍未得到清晰阐明。TOX是淋巴组织诱导细胞（一种参与淋巴结器官发生的3型固有淋巴样细胞（ILC3））以及自然杀伤细胞（natural killer cells, NK，属于1型固有淋巴样细胞（ILC1））发育所必需的调控因子。本研究证实，多谱系固有淋巴样细胞的生成依赖于TOX，这缘于依赖TOX的固有淋巴样细胞通用祖细胞（common ILC progenitors）发育过程。比较转录组分析显示，在缺失TOX的情况下，固有淋巴样细胞基因程序的诸多环节无法正常激活，提示该核因子是固有淋巴样细胞谱系特化的关键早期决定因子。实验分为TOX敲除（TOX KO）组与野生型（wild type）组。