We have examined the effect of FoxP3 on class I gene expression both in vivo and in cell culture. In cell culture assays, FoxP3 has a dramatic effect on MHC class I promoter activity. However, the effect is cell type dependent. Thus, FoxP3 enhances promoter activity in Jurkat T cells but inhibits it in Hela epithelial cells. Although only a single canonical FoxP3 binding site occurs within the promoter, multiple response elements have been mapped in both cell types. Intriguingly, the single FoxP3 binding site is located within the IRE of the promoter, such that mutation of the IRE abrogates the FoxP3 response. Furthermore, although FoxP3 is known to interact with RUNX1 and RUNX1 enhances class I promoter activity, the two factors function independently. Most intriguingly and consistent with the cell culture findings, class I expression in Tregs in vivo is elevated relative to the CD4+CD25- T cell subset. The functional significance of this over-expression, if any, is being pursued.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011425-02
Application #
8763515
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2013
Total Cost
$163,447
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Mu, Jie; Tai, Xuguang; Iyer, Shankar S et al. (2014) Regulation of MHC class I expression by Foxp3 and its effect on regulatory T cell function. J Immunol 192:2892-903