妊娠阶段中FOXP3的翻译后修饰作用:基因重编程及调节网络

Post-translational modification of FOXP3 in pregnancy:Gene reprogramming and regulatory networks

正常妊娠过程的维持需要各种细胞与细胞因子等相互调节构成一个母胎界面免疫微环境调节网络,然而,母胎免疫微环境中细胞组分的变化和基因组的表观遗传修饰的调控引起了人们的广泛关注。从表观遗传修饰的角度出发去理解正常妊娠过程所需的各种适当的转录调控模式,有利于进一步探索对妊娠并发症发病机制的新的理解。Treg细胞被赋予了独特的过程来快速响应妊娠免疫微环境的动态变化,并可以通过不同的机制来调节基因特异性转录和翻译过程。对妊娠所必需的Treg细胞,本文从不同的表观修饰层面进行了描述,并对FOXP3蛋白参与Treg功能调控的翻译后修饰的研究现状进行了详细说明。本综述主要从女性生殖细胞发育、胚胎发育、胎儿生长、正常妊娠维持和妊娠并发症这几个方面对FOXP3翻译后修饰的作用位点进行探索,并尝试对FOXP3所调控的Treg翻译后修饰状态进行重新定义,为妊娠并发症的个性化诊断和治疗提供了新见解。

The maintenance of normal pregnancy requires the mutual regulation of various cells and cytokines,etc.to form a maternal-fetal interface immune microenvironment regulatory network.However,the regulation of cell component changes and genome epigenetic modifications in the maternal-fetal immune micro-environment has attracted extensive attention.Understanding the appropriate transcriptional regulation modes required for normal pregnancy process from the perspective of epigenetic modification is conducive to further exploring new understanding of the pathogenesis of pregnancy complications.Treg cells are endowed with unique processes to rapidly respond to dynamic changes in the immune microenvironment of pregnancy and can regulate gene-specific transcription and translation processes through different mechanisms.We also described the different epigenetic modification levels of Treg cells essential for pregnancy,and detailed the current research status of FOXP3 protein involved in post-translational modification of Treg function regulation.This review mainly explored the action sites of FOXP3 post-translational modification from the aspects of female germ-cell development,embryonic development,fetal growth,normal pregnancy maintenance and pregnancy complications,and attempted to redefine the post-translational modification state of Treg regulated by FOXP3,providing new insights for personalized diagnosis and treatment of pregnancy complications.