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

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-γ in NK cells during our gene screening work. In present study, we investigate the relationship between HMBOX1 and IFN-γ 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-γ. Subsequently, over-expression of HMBOX1 significantly inhibited the expression and production of IFN-γ 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-γ promoter. These findings indicated that HMBOX1 may function as a negative regulator of IFN-γ in NK cells.