HMBOX1, homeobox transcription factor, negatively regulates interferon-gamma production in natural killer cells.

摘要

HMBOX1 is a new member of homeobox family and predicted to be a transcriptional repressor, its function in NK cells is completely unclear. Previously we found that overexpression of HMBOX1 downregulated mRNA level of IFN-gamma in NK cells during our gene screening work. In present study, we investigate the relationship between HMBOX1 and IFN-gamma in detail. Firstly, we describe the properties of HMBOX1 gene transcription in activated NK cells, and found that the transcriptional levels of HMBOX1 were significantly decreased in NK cells after activated by IL-2, IL-15 and IL-12, which was opposite to the expression profile of IFN-gamma. Subsequently, over-expression of HMBOX1 significantly inhibited the expression and production of IFN-gamma in NK cells in response to the stimulation of tumor cell K562 or PMA/ionomycin. Additionally, by luciferase reporter assay, HMBOX1 displayed suppressive effect on the transcription activity of IFN-gamma promoter. These findings indicated that HMBOX1 may function as a negative regulator of IFN-gamma in NK cells.