High-Dose Interferon-γ Promotes Abortion in Mice by Suppressing Treg and Th17 Polarization

As a classic type I cytokine, interferon-gamma (IFN-) 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/cxBALB/c) mice were subjected to intravaginal IFN- administration (5x10(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- 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- receptor alpha (IFN-R) level was also lowered in the uterus. These results demonstrate that in murine pregnancy, a supraphysiological dose of IFN- 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-R, may be one of the main reasons that IFN- causes abortion.