High-dose interferon-γ promotes abortion in mice by suppressing Treg and Th17 polarization

As a classic type I cytokine, interferon-gamma (IFN-γ) is known to manifest a miscarriage-inducing effect, although the specific mechanism is still unclear. To determine whether immune cells such as regulatory T (Treg) and Th17 cells are involved in these abortions, syngeneically pregnant (BALB/c×BALB/c) mice were subjected to intravaginal IFN-γ administration (5 × 10(3) IU/mouse on D3 of gestation). These mice experienced significant fetal loss on D7/D8 of pregnancy, and a remarkable drop in the Treg cell ratio was observed in the peripheral blood and the spleen by flow cytometry. In situ detection of the uterine tissue peri-implantation revealed that IFN-γ treatment also caused statistically significant reductions in forkhead box P3, RAR-related orphan receptor gamma, and IL-17 levels, which indicated local decreases in Treg and Th17 cells at uterine implantation sites. The IFN-γ receptor alpha (IFN-γRα) level was also lowered in the uterus. These results demonstrate that in murine pregnancy, a supraphysiological dose of IFN-γ could induce peri-implantation failure. Moreover, in this study, the decreases in both Treg and Th17-type cells, which may be relevant to the role of IFN-γRα, may be one of the main reasons that IFN-γ causes abortion.