Toxoplasma gondii excreted-secreted antigens suppress Foxp3 promoter activity via a SP1-dependent mechanism.

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.

• Authors: Jinling Chen, Jingjing Wang, Xuyang Gao, Dandan Zhu, Liuting Chen, Yinong Duan
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 18 Pg. 10785-10791 (09 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 32729205 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Antigens, Protozoan
• Forkhead Transcription Factors
• Foxp3 protein, mouse
• Recombinant Proteins
• Sp1 Transcription Factor
• excretory-secretory antigen, Toxoplasma

Topics

• Animals
• Antigens, Protozoan (immunology)
• Base Sequence
• Binding Sites
• Cell Line, Tumor
• Forkhead Transcription Factors (biosynthesis, genetics)
• Gene Expression Regulation, Neoplastic (genetics, immunology)
• Genes, Reporter
• Mice
• Promoter Regions, Genetic (genetics)
• Recombinant Proteins (metabolism)
• Sp1 Transcription Factor (physiology)
• T-Lymphocytes, Regulatory (immunology, metabolism)
• Toxoplasma (immunology)