Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Immunity. 2013 Apr 18;38(4):681-93. doi: 10.1016/j.immuni.2013.01.010. Epub 2013 Apr 4.
How innate lymphoid cells (ILCs) in the thymus and gut become specialized effectors is unclear. The prototypic innate-like γδ T cells (Tγδ17) are a major source of interleukin-17 (IL-17). We demonstrate that Tγδ17 cells are programmed by a gene regulatory network consisting of a quartet of high-mobility group (HMG) box transcription factors, SOX4, SOX13, TCF1, and LEF1, and not by conventional TCR signaling. SOX4 and SOX13 directly regulated the two requisite Tγδ17 cell-specific genes, Rorc and Blk, whereas TCF1 and LEF1 countered the SOX proteins and induced genes of alternate effector subsets. The T cell lineage specification factor TCF1 was also indispensable for the generation of IL-22 producing gut NKp46(+) ILCs and restrained cytokine production by lymphoid tissue inducer-like effectors. These results indicate that similar gene network architecture programs innate sources of IL-17, independent of anatomical origins.
先天淋巴样细胞（ILCs）在胸腺和肠道中如何成为特化效应细胞尚不清楚。典型的先天样 γδ T 细胞（Tγδ17）是白细胞介素 17（IL-17）的主要来源。我们证明，Tγδ17 细胞由一个由四个高迁移率族（HMG）框转录因子（SOX4、SOX13、TCF1 和 LEF1）组成的基因调控网络编程，而不是通过传统的 TCR 信号。SOX4 和 SOX13 直接调节两个必需的 Tγδ17 细胞特异性基因，Rorc 和 Blk，而 TCF1 和 LEF1 则对抗 SOX 蛋白并诱导替代效应细胞亚群的基因。T 细胞谱系特异性因子 TCF1 对于产生产生 IL-22 的肠道 NKp46（+）ILC 也是必不可少的，并且限制了淋巴组织诱导样效应细胞的细胞因子产生。这些结果表明，类似的基因网络架构程序先天产生 IL-17，与解剖起源无关。
