Gfi1, a transcriptional repressor, inhibits the induction of the T helper type 1 programme in activated CD4 T cells
Gfi1, a transcriptional repressor, inhibits the induction of the T helper type 1 programme in activated CD4 T cells
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DOI：
10.1111/imm.12580
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发表时间：
2016-04-01
期刊：
影响因子：
6.4
通讯作者：
Yamashita, Masakatsu
中科院分区：
文献类型：
--
作者：
Suzuki, Junpei;Maruyama, Saho;Yamashita, Masakatsu
转录抑制因子 Gfi1 促进 2 型辅助 T (Th2) 细胞发育并抑制 Th17 和诱导性调节性 T 细胞分化。然而，Gfi1在调节Th1细胞分化和Th1型免疫反应中的作用仍有待研究。我们在此证明 Gfi1 抑制活化 CD4 T 细胞中 Th1 程序的诱导。活化的 Gfi1 缺陷型 CD4 T 细胞以不依赖白细胞介素 12 和干扰素 γ 的方式自发发育为 Th1 细胞。使用镍过敏和迟发型超敏反应 (DTH) 小鼠模型，在 Gfi1 缺陷小鼠体内证实了 Th1 型免疫反应的增加。发现 Gfi1 缺陷的活化 CD4 T 细胞中 Th1 相关转录因子的表达水平增加。 Tbx21、Eomes 和 Runx2 被确定为 Gfi1 可能的直接靶标。 Gfi1 与 Tbx21、Eomes 和 Runx2 基因位点结合，部分通过调节 Lsd1 招募来降低组蛋白 H3K4 甲基化水平。总之，这些发现证明了 Gfi1 在调节 Th1 型免疫反应中的新调节作用。
A transcriptional repressor Gfi1 promotes T helper type 2 (Th2) cell development and inhibits Th17 and inducible regulatory T-cell differentiation. However, the role of Gfi1 in regulating Th1 cell differentiation and the Th1-type immune response remains to be investigated. We herein demonstrate that Gfi1 inhibits the induction of the Th1 programme in activated CD4 T cells. The activated Gfi1-deficient CD4 T cells spontaneously develop into Th1 cells in an interleukin-12-and interferon-gamma-independent manner. The increase of Th1-type immune responses was confirmed in vivo in Gfi1-deficient mice using a murine model of nickel allergy and delayed-type hypersensitivity (DTH). The expression levels of Th1-related transcription factors were found to increase in Gfi1-deficient activated CD4 T cells. Tbx21, Eomes and Runx2 were identified as possible direct targets of Gfi1. Gfi1 binds to the Tbx21, Eomes and Runx2 gene loci and reduces the histone H3K4 methylation levels in part by modulating Lsd1 recruitment. Together, these findings demonstrate a novel regulatory role of Gfi1 in the regulation of the Th1-type immune response.