当前位置: X-MOL 学术J. Cell. Mol. Med. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Toxoplasma gondii excreted-secreted antigens suppress Foxp3 promoter activity via a SP1-dependent mechanism.
Journal of Cellular and Molecular Medicine ( IF 4.3 ) Pub Date : 2020-07-29 , DOI: 10.1111/jcmm.15703
Jinling Chen 1 , Jingjing Wang 1 , Xuyang Gao 1 , Dandan Zhu 1 , Liuting Chen 1 , Yinong Duan 1
Affiliation  

Toxoplasma gondii excreted‐secreted antigens (ESA) could result in adverse outcomes of pregnancy including abortion, stillbirth, foetal infection or teratogenesis in mice during early stage of pregnancy. Defective generation or function of regulatory T cells (Tregs) may account for those adverse pregnancy outcomes. Forkhead box p3 (Foxp3), which is the key transcriptional factor of Tregs, modulates its development and maintains inhibitory function. We previously demonstrated that ESA inhibited Foxp3 expression by attenuating transforming growth factor β RII/Smad2/Smad3/Smad4 pathway. In this study, we propose to study the role of ESA on the activity of Foxp3 promoter and explore potential mechanisms. We demonstrated that ESA suppressed Foxp3 promoter activity using dual‐luciferase reporter assay. ESA functioned at −443/−96 region of Foxp3 promoter to suppress its activity using truncated fragments of Foxp3 promoter. Further analysis revealed that suppressive role of ESA on Foxp3 promoter activity is related to specificity protein 1 (SP1). Transfection of expression plasmid of pcDNA3.1‐SP1 could restore the down‐regulation of Foxp3 induced by ESA. In conclusion, this study provides a new mechanism by which ESA could inhibit the Foxp3 promoter activity via SP1.

中文翻译:


弓形虫分泌的抗原通过 SP1 依赖性机制抑制 Foxp3 启动子活性。



弓形虫分泌抗原(ESA)可能导致妊娠早期小鼠的不良妊娠结局,包括流产、死产、胎儿感染或致畸。调节性 T 细胞 (Treg) 的生成或功能缺陷可能是导致不良妊娠结局的原因。 Forkhead box p3 (Foxp3) 是 Tregs 的关键转录因子,调节其发育并维持抑制功能。我们之前证明ESA通过减弱转化生长因子βRII/Smad2/Smad3/Smad4途径抑制Foxp3表达。在本研究中,我们拟研究ESA对Foxp3启动子活性的作用并探索潜在的机制。我们使用双荧光素酶报告基因测定证明 ESA 抑制 Foxp3 启动子活性。 ESA 在 Foxp3 启动子的 -443/-96 区域发挥作用,利用 Foxp3 启动子的截短片段抑制其活性。进一步分析发现,ESA对Foxp3启动子活性的抑制作用与特异性蛋白1(SP1)有关。转染pcDNA3.1-SP1表达质粒可以恢复ESA诱导的Foxp3下调。总之,本研究提供了ESA通过SP1抑制Foxp3启动子活性的新机制。
更新日期:2020-09-28
down
wechat
bug