Interferon-γ-activated human leukocyte antigen-G gene expression in placenta-derived multipotent cells involves the epigenetic control and transcriptional regulation (167.12)

Abstract

Abstract Placenta-derived multipotent cells (PDMCs) are progenitor cells isolated from the human term placenta with differentiation capacity for all three germ layers as well as strong immunomodulatory properties. The placenta is central to maintaining fetomaternal tolerance, and one of the most important immunomodulatory molecules involved is the human leukocyte antigen-G (HLA-G). HLA-G is a non-classical major hisotocompatibility complex (MHC) class I molecule which exhibits a restricted tissue-specific expression and exerts multiple immuneregulatory functions for maintaining the tolerance of placenta. We have shown that PDMCs can resist natural killer (NK) cell-mediated cytotoxicity by interferon-γ (IFN-γ)-induced surface HLA-G expression, suggesting that the expression of HLA-G may be involved the cis-acting epigenetic control and transcriptional regulation. Recently, we found that IFN-γ induces the expression of IFN regulatory factor 1 (IRF-1) and phosphorylation of STAT-1 in PDMCs. We speculate that the control of HLA-G in PDMCs involved not only the IFN-γ cis-acting regulatory elements including the IFN-stimulated response element (ISRE) and IFN-γ activation site (GAS), but also DNA-methylation which synergistically render the HLA-G gene promoter highly responsive to IFN-γ. Taken together, our results indicate that IFN-γ-activated HLA-G gene expression in PDMCs is involved the cis-acting epigenetic control and transcriptional regulation through JAK/STAT-1 signaling pathway.