Histone deacetylase 3 contributes to the antiviral innate immunity of macrophages by interacting with FOXK1 to regulate STAT1/2 transcription.
Histone deacetylase 3 contributes to the antiviral innate immunity of macrophages by interacting with FOXK1 to regulate STAT1/2 transcription.
复制标题
DOI：
10.1016/j.celrep.2022.110302
复制
发表时间：
2022-01
期刊：
影响因子：
8.8
通讯作者：
Liping Yang;Shengchuan Chen;Qun Zhao;Chaohu Pan;Linan Peng;Yu Han;Lili Li;Jiayin Ruan;
中科院分区：
文献类型：
--
作者：
Liping Yang;Shengchuan Chen;Qun Zhao;Chaohu Pan;Linan Peng;Yu Han;Lili Li;Jiayin Ruan;
众所周知，干扰素（IFN）-α/-β通过诱导IFN刺激基因（ISG）激活JAK/STAT信号通路并抑制病毒复制。在这里，我们报告了从巨噬细胞中敲除HDAC 3导致STAT 1和STAT 2表达降低，导致细胞和小鼠抗病毒免疫缺陷。进一步的研究表明，HDAC 3与保守的转录因子叉头盒K1（FOXK 1）相互作用，与FOXK 1共定位在STAT 1和STAT 2的启动子处，并且是保护FOXK 1免受溶酶体系统介导的降解所必需的。FOXK 1缺陷型巨噬细胞也表现出低STAT 1和STAT 2表达，对病毒的反应有缺陷。因此，我们的研究揭示了HDAC 3通过与FOXK 1相互作用调节STAT 1和STAT 2的表达来调节巨噬细胞的抗病毒免疫的生物学重要性。
It is well known that interferon (IFN)-α/-β activates the JAK/STAT signaling pathway and suppresses viral replication through the induction of IFN stimulated genes (ISGs). Here, we report that knockout of HDAC3 from macrophages results in the decreased expression of STAT1 and STAT2, leading to defective antiviral immunity in cells and mice. Further studies show that HDAC3 interacts with a conserved transcription factor Forkhead Box K1 (FOXK1), co-localizes with FOXK1 at the promoter of STAT1 and STAT2, and is required for protecting FOXK1 from lysosomal system-mediated degradation. FOXK1-deficient macrophages also show low STAT1 and STAT2 expression with defective responses to viruses. Thus, our studies uncover the biological importance of HDAC3 in regulating the antiviral immunity of macrophages through interacting with FOXK1 to regulate the expression of STAT1 and STAT2.