FOXP3调控中的表观遗传学现象

Epigenetic phenomena associated with FOXP3

FOXP3转录因子是维持调节性T细胞(Treg)免疫抑制功能的必要条件。研究发现FOXP3也可在抗原受体激活的非调节性T细胞表达,使其作为Treg的特异性标志受到质疑。实验证明Treg细胞的FOXP3基因座含有多个去甲基化区域,且似乎更有特异性。FOXP3基因表达和蛋白功能发挥随着组蛋白甲基化和乙酰化水平而改变。DNA甲基化转移酶抑制剂(DNMTi)或组蛋白去乙酰化酶抑制剂(HDACi)可诱导具有免疫抑制功能的Treg产生。本文对FOXP3基因表达调控,蛋白修饰后调节其它基因表达过程中的表观遗传学现象及临床应用前景作一综述。

FOXP3,a transcript factor,is necessary and sufficient for induction and persistence of the immunosuppressive of regulatory T cells（Tregs）.Recent datas indicate FOXP3 can also be transiently expressed in T cell antigen receptor-activated human non-regulatory cells,which makes FOXP3 as the specific marker of Tregs questioned.Further experiments have proved that Tregs cells contain several specific demethylation areas（TSDRs） in FOXP3 gene locus.The methylation status of these TSDRs seems to be a more specific marker.Additionally,FOXP3 gene expression and its protein function involve histone methylation and acetylation.Tregs with immune suppression can be induced by DNA methyltransferase inhibitors or histone deacetylase inhibitors（HDACi）.This review will focus on epigenetic phenomena in the process of FOXP3 gene expression,post-translational modification,and regulation of other genes＇ expression by FOXP3 protein,as well as its possible clinical application.