Expression of Interferon by Decidual Cells and Natural Killer Cells at the Human Implantation Site: Implications for Preeclampsia, Spontaneous Abortion, and Intrauterine Growth Restriction

Human first-trimester decidual cells (FTDCs) chemoattract CXCR3-expressing circulating CD56(bright)CD16(-) natural killer (NK) cells, which increase uteroplacental blood flow by remodeling spiral arteries and arterioles. This recruitment reflects elevated FTDC expression of NK cell-recruiting induced protein 10 and interferon (IFN)-inducible T-cell- chemoattractant produced in response to the synergistic effects of tumor necrosis factor (TNF-) and IFN- stimulation. Decidual macrophages express TNF-, whereas the cellular origin of IFN- is unclear. Therefore, this study aims to identify the cell source(s) of IFN- in human first trimester decidua. Immunostaining of decidual sections revealed that both FTDCs and decidual NK (dNK) cells express IFN-. Although individual dNK cells express higher IFN- levels, the more numerous FTDCs account for greater proportion of total IFN- immunostaining. Freshly isolated FTDCs express greater IFN- staining than dNK cells as measured by flow cytometry, whereas incubation of dNK cells with documented NK cell activators significantly increases IFN- above FTDC levels. Confluent FTDCs intrinsically produce, but paradoxically respond to, exogenous IFN-.