Blimp-1/PRDM1 is a critical regulator of Type III Interferon responses in mammary epithelial cells
Blimp-1/PRDM1 is a critical regulator of Type III Interferon responses in mammary epithelial cells
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DOI：
10.1038/s41598-017-18652-9
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发表时间：
2018-01-10
影响因子：
4.6
通讯作者：
Mould, Arne W.
中科院分区：
文献类型：
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作者：
Elias, Salah;Robertson, Elizabeth J.;Mould, Arne W.
转录抑制因子 Blimp-1 最初被克隆为 I 型干扰素 (IFN)-β 基因表达的沉默子，控制多种组织环境中的细胞命运决定。最近显示乳腺的条件失活会破坏上皮细胞结构。在这里，我们报道，Blimp-1 调节病毒防御、IFN 信号传导和 MHC I 类途径的表达，并直接靶向转录激活因子 Stat1。乳腺上皮细胞 (MEC) 3D 培养物中的 Blimp-1 功能丧失导致 dsRNA 积累和 III 型 IFN-lambda 表达。用 IFN lambda 处理的培养物同样表现出管腔形成缺陷。这些结果表明 III 型 IFN-lambda 深刻影响 MEC 的行为，并将 Blimp-1 确定为 IFN 信号级联的关键调节因子。
The transcriptional repressor Blimp-1 originally cloned as a silencer of type I interferon (IFN)-beta gene expression controls cell fate decisions in multiple tissue contexts. Conditional inactivation in the mammary gland was recently shown to disrupt epithelial cell architecture. Here we report that Blimp-1 regulates expression of viral defense, IFN signaling and MHC class I pathways, and directly targets the transcriptional activator Stat1. Blimp-1 functional loss in 3D cultures of mammary epithelial cells (MECs) results in accumulation of dsRNA and expression of type III IFN-lambda. Cultures treated with IFN lambda similarly display defective lumen formation. These results demonstrate that type III IFN-lambda profoundly influences the behavior of MECs and identify Blimp-1 as a critical regulator of IFN signaling cascades.