Open AccessToxoplasma gondii excreted‐secreted antigens suppress Foxp3 promoter activity via a SP1‐dependent mechanism
Author(s) -
Chen Jinling,
Wang Jingjing,
Gao Xuyang,
Zhu Dandan,
Chen Liuting,
Duan Yig
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15703
Subject(s) - foxp3 , toxoplasma gondii , luciferase , transfection , biology , microbiology and biotechnology , chemistry , immunology , antibody , gene , immune system , genetics
Abstract 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.