| THEMIS(Thymus expressed molecule involved in selection)plays an important role in T cell development via TCR signaling regulation.THEMIS is mainly expressed in T cells.During T cell development,THEMIS expression is first detected in DN cells,reach its peak level in DP cells,and gradually decrease in mature CD4+/CD8+SP cells and peripheral T cells.Although,it is well known that THEMIS is required for T cell development,the molecular mechanism and functional domain responsible for its differential expression in T cell subsets are still unclear.Forkhead Box Protein3(FOXP3),is considered to be a specific transcription factor of CD4+ CD25+Treg cells,FOXP3 involved in the regulation of immune response and maintenance of Treg phenotypes.Previous study found that the expression of FOXP3 can repress the transcription of many genes,involved in TCR signaling pathways,such as THEMIS.However,the mechanism of how FOXP3 regulates THEMIS transcription is not understood.To explore the relationship between FOXP3 and THEMIS,and elucidate the potential molecular mechanism will undoublty contribute to a better understanding of THEMIS's tissue and cell type specificity.In this study,we used a series of molecular biology methods to investigate the transcriptional control of THEMIS in Jurkat T cell line under PMA/ionomycin stimulation.We confirmed that THEMIS had a strict cell and tissue specificity,and we further defined the localization of human THEMIS core promoter.We also observed that FOXP3 inhibits THEMIS expression induced by PMA/ionomycin,but the inhibition is not dependent on the direct binding to the THEMIS promoter.Instead we found that p65,a subunit of NF-?B,can increase THEMIS expression by directiy binding to its core promoter,we also showed that FOXP3 overexpression decreased THEMIS expression by reducing p65 translocation and finally affected the binding of p65 to the THEMIS promoter.This work will provide a theoretical basis for further research. |
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