A network of high-mobility group box transcription factors programs innate interleukin-17 production.

A network of high-mobility group box transcription factors programs innate interleukin-17 production.
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DOI:
10.1016/j.immuni.2013.01.010
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发表时间:
2013-04-18
期刊:
影响因子:
32.4
通讯作者:
Immunological Genome Project Consortium
Immunological Genome Project Consortium
中科院分区:
医学1区
文献类型:
--
作者:
Malhotra N;Narayan K;Cho OH;Sylvia KE;Yin C;Melichar H;Rashighi M;Lefebvre V;Harris JE;Berg LJ;Kang J;Immunological Genome Project Consortium

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胸腺和肠道中的固有淋巴样细胞(ILCs)如何成为特殊的效应器尚不清楚。先天类γδT细胞(Tγδ17)是白介素17(IL 17)的主要来源。我们证明Tγδ17细胞是由一个由高迁移率族框转录因子SOX4、SOX13、TCF1和LEF1组成的基因调控网络编程的,而不是通过传统的TCRs信号。SOX4和SOX13直接调控两个必需的Tγδ17细胞特异性基因RORC和BLK,而TCF1和LEF1对抗SOX蛋白和诱导交替效应亚群的基因。T细胞谱系指定因子TCF1对于产生IL-22的肠道NKp46+ILCs和抑制淋巴组织诱导器样效应细胞的细胞因子的产生也是不可或缺的。这些结果表明,类似的基因网络结构程序与生俱来的IL-17来源,与解剖来源无关。
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 box (HMG) 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.
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