Laboratory of Experimental Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
Nat Commun. 2019 Feb 1;10(1):549. doi: 10.1038/s41467-019-08404-w.
The genome organizer, special AT-rich sequence-binding protein-1 (Satb1), plays a pivotal role in the regulation of global gene networks in a cell type-dependent manner and is indispensable for the development of multiple cell types, including mature CD4 T, CD8 T, and Foxp3 regulatory T cells in the thymus. However, it remains unknown how the differentiation and effector program of the Th subsets in the periphery are regulated by Satb1. Here, we demonstrate that Satb1 differentially regulates gene expression profiles in non-pathogenic and pathogenic Th17 cells and promotes the pathogenic effector program of encephalitogenic Th17 cells by regulating GM-CSF via Bhlhe40 and inhibiting PD-1 expression. However, Satb1 is dispensable for the differentiation and non-pathogenic functions of Th17 cells. These results indicate that Satb1 regulates the specific gene expression and function of effector Th17 cells in tissue inflammation.
基因组组织者，富含特殊 AT 的序列结合蛋白-1（Satb1），以细胞类型依赖的方式在调节全局基因网络中发挥关键作用，对于包括成熟 CD4 T、CD8 T 和胸腺中 Foxp3 调节性 T 细胞在内的多种细胞类型的发育是必不可少的。然而，Satb1 如何调节外周 Th 亚群的分化和效应程序仍然未知。在这里，我们证明 Satb1 以不同的方式调节非致病性和致病性 Th17 细胞中的基因表达谱，并通过 Bhlhe40 调节 GM-CSF 和抑制 PD-1 表达来促进致脑炎 Th17 细胞的致病性效应程序。然而，Satb1 对于 Th17 细胞的分化和非致病性功能是可有可无的。这些结果表明 Satb1 调节组织炎症中效应性 Th17 细胞的特定基因表达和功能。
