Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Immunity. 2014 Jun 19;40(6):865-79. doi: 10.1016/j.immuni.2014.03.014. Epub 2014 May 22.
Specification of the T helper 17 (Th17) cell lineage requires a well-defined set of transcription factors, but how these integrate with posttranscriptional and epigenetic programs to regulate gene expression is poorly understood. Here we found defective Th17 cell cytokine expression in miR-155-deficient CD4+ T cells in vitro and in vivo. Mir155 was bound by Th17 cell transcription factors and was highly expressed during Th17 cell differentiation. miR-155-deficient Th17 and T regulatory (Treg) cells expressed increased amounts of Jarid2, a DNA-binding protein that recruits the Polycomb Repressive Complex 2 (PRC2) to chromatin. PRC2 binding to chromatin and H3K27 histone methylation was increased in miR-155-deficient cells, coinciding with failure to express Il22, Il10, Il9, and Atf3. Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence of Mir155 could be partially suppressed by Jarid2 deletion. Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.
辅助性 T 细胞 17（Th17）细胞谱系的特异性需要一组明确的转录因子，但这些转录因子如何与转录后和表观遗传程序整合以调节基因表达还知之甚少。在这里，我们发现 miR-155 缺陷的 CD4+T 细胞在体外和体内的 Th17 细胞细胞因子表达缺陷。Th17 细胞转录因子结合 Mir155，在 Th17 细胞分化过程中高表达。miR-155 缺陷的 Th17 和 T 调节（Treg）细胞表达增加的 Jarid2，一种募集多梳抑制复合物 2（PRC2）到染色质的 DNA 结合蛋白。PRC2 与染色质的结合和 H3K27 组蛋白甲基化在 miR-155 缺陷细胞中增加，与 Il22、Il10、Il9 和 Atf3 的表达失败同时发生。在没有 Mir155 的情况下，Th17 细胞细胞因子表达和 Treg 细胞动态平衡的缺陷可以通过 Jarid2 的缺失部分抑制。因此，miR-155 通过抑制 Jarid2 的抑制作用促进 Th17 细胞的功能。
