Cutting Edge: The Expression of Transcription Inhibitor GFI1 Is Induced by Retinoic Acid to Rein in Th9 Polarization.

Cutting Edge: The Expression of Transcription Inhibitor GFI1 Is Induced by Retinoic Acid to Rein in Th9 Polarization.
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DOI:
10.4049/jimmunol.2200328
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发表时间:
2022-10-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Kim CH
Kim CH
中科院分区:
其他
文献类型:
--
作者:
Friesen L;Kostlan R;Liu Q;Yu H;Zhu J;Lukacs N;Kim CH

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IL-9主要由特化T细胞、肥大细胞和ILC 2产生,调节免疫应答,包括抗蠕虫和过敏应答。幼稚CD 4 T细胞极化为产生IL 9的T细胞(Th 9)由IL-4和TGF-β1或IL-1β诱导。在这里,我们报告说,转录因子GFI 1在小鼠Th 9极化中起着负作用。此外,GFI 1的表达受配体RARα的控制,从而允许GFI 1介导视黄酸对IL-9表达的负作用。Gfi 1基因在启动子区具有多个RARα结合位点,用于以视黄酸依赖性方式招募核辅激活因子SRC 3和p300进行组蛋白表观遗传修饰。视黄酸诱导的GFI 1结合Il 9基因并抑制其表达。因此,GFI 1是一种新的IL 9基因表达的负调控因子。IL-9调节的负GFI 1途径为Th 9活性提供了潜在的控制点。
IL-9, produced mainly by specialized T cells, mast cells and ILC2, regulates immune responses including anti-helminth and allergic responses. Polarization of naïve CD4 T cells into IL9-producing T cells (Th9) is induced by IL-4 and TGF-β1 or IL-1β. Here, we report that the transcription factor GFI1 plays a negative role in mouse Th9 polarization. Moreover, the expression of GFI1 is controlled by liganded RARα, allowing GFI1 to mediate the negative effect of retinoic acid on IL-9 expression. The Gfi1 gene has multiple RARα binding sites in the promoter region for recruiting nuclear coactivator SRC3 and p300 for histone epigenetic modifications in a retinoic acid-dependent manner. Retinoic acid-induced GFI1 binds the Il9 gene and suppresses its expression. Thus, GFI1 is a novel negative regulator of Il9 gene expression. The negative GFI1 pathway for IL-9 regulation provides a potential control point for Th9 activity.
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