Seehus Corey R, Aliahmad Parinaz, de la Torre Brian, Iliev Iliyan D, Spurka Lindsay, Funari Vincent A, Kaye Jonathan
Research Division of Immunology, Departments of Biomedical Sciences and Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Nat Immunol. 2015 Jun;16(6):599-608. doi: 10.1038/ni.3168. Epub 2015 Apr 27.
Diverse innate lymphoid cell (ILC) subtypes have been defined on the basis of effector function and transcription factor expression. ILCs derive from common lymphoid progenitors, although the transcriptional pathways that lead to ILC-lineage specification remain poorly characterized. Here we found that the transcriptional regulator TOX was required for the in vivo differentiation of common lymphoid progenitors into ILC lineage-restricted cells. In vitro modeling demonstrated that TOX deficiency resulted in early defects in the survival or proliferation of progenitor cells, as well as ILC differentiation at a later stage. In addition, comparative transcriptome analysis of bone marrow progenitors revealed that TOX-deficient cells failed to upregulate many genes of the ILC program, including genes that are targets of Notch, which indicated that TOX is a key determinant of early specification to the ILC lineage.
不同的固有淋巴细胞（ILC）亚型已根据效应功能和转录因子表达进行了定义。ILC来源于共同淋巴祖细胞，尽管导致ILC谱系特化的转录途径仍未得到充分表征。在这里，我们发现转录调节因子TOX是共同淋巴祖细胞在体内分化为ILC谱系受限细胞所必需的。体外模型表明，TOX缺陷导致祖细胞在存活或增殖方面出现早期缺陷，以及后期ILC分化出现缺陷。此外，对骨髓祖细胞的比较转录组分析表明，缺乏TOX的细胞未能上调许多ILC程序基因，包括Notch靶基因，这表明TOX是ILC谱系早期特化的关键决定因素。
