Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua
Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua
复制标题
DOI：
10.1038/s41598-020-62593-9
复制
发表时间：
2020-04-01
影响因子：
4.6
通讯作者：
Mor, Gil
中科院分区：
文献类型：
--
作者：
Silasi, Michelle;You, Yuan;Mor, Gil
着床、滋养细胞侵袭和胎盘形成的过程需要滋养细胞（胚胎）和蜕膜（母体）之间不断的适应和修饰。在蜕膜内，随着妊娠的进展，母体免疫系统在细胞群、表型和免疫因子、细胞因子和趋化因子的产生方面发生了持续的变化。人绒毛膜促性腺激素（hCG）是囊胚最早产生的激素之一，具有强大的免疫调节作用，特别是与T细胞有关。我们假设滋养细胞衍生的hCG通过改变基质/蜕膜细胞产生的细胞因子谱来调节存在于母胎界面的免疫群体。通过个体样本的体外模型，我们证明hCG通过诱导H3K27me3组蛋白甲基化来抑制CXCL10的表达，该甲基化与CXCL10启动子的4区结合，从而抑制其表达。hcg诱导的组蛋白甲基化是通过EZH2介导的，EZH2是PRC2复合体的一个功能成员。CXCL10表达的调控对子宫内膜基质细胞募集CD8细胞的能力有重要影响。我们证明了胎盘（hCG）和蜕膜（CXCL10）之间的串扰在控制免疫细胞募集中存在。这种免疫调节功能的改变，例如在感染期间，将对怀孕的成功产生不利影响。
The process of implantation, trophoblast invasion and placentation demand continuous adaptation and modifications between the trophoblast (embryonic) and the decidua (maternal). Within the decidua, the maternal immune system undergoes continued changes, as the pregnancy progress, in terms of the cell population, phenotype and production of immune factors, cytokines and chemokines. Human chorionic gonadotropin (hCG) is one of the earliest hormones produced by the blastocyst and has potent immune modulatory effects, especially in relation to T cells. We hypothesized that trophoblast-derived hCG modulates the immune population present at the maternal fetal interface by modifying the cytokine profile produced by the stromal/decidual cells. Using in vitro models from decidual samples we demonstrate that hCG inhibits CXCL10 expression by inducing H3K27me3 histone methylation, which binds to Region 4 of the CXCL10 promoter, thereby suppressing its expression. hCG-induced histone methylation is mediated through EZH2, a functional member of the PRC2 complex. Regulation of CXCL10 expression has a major impact on the capacity of endometrial stromal cells to recruit CD8 cells. We demonstrate the existence of a cross talk between the placenta (hCG) and the decidua (CXCL10) in the control of immune cell recruitment. Alterations in this immune regulatory function, such as during infection, will have detrimental effects on the success of the pregnancy.