title: High-dose interferon-γ promotes abortion in mice by suppressing Treg and Th17 polarization.
abstract: 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.
authors.affiliation: 1 State Key Laboratory of Reproductive Biology, Institute of Zoology , Chinese Academy of Sciences, Beijing, P.R. China .
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Liu
authors.forename: Zhen-Kun
authors.initials: ZK
authors.lastname: Liu
authors.forename: Huhe
authors.initials: H
authors.lastname: Chao
authors.forename: Zhongyin
authors.initials: Z
authors.lastname: Li
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Song
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Jing-Pian
authors.initials: JP
authors.lastname: Peng
mesh_terms: D000028:Abortion, Induced; D000818:Animals; D018791:CD4 Lymphocyte Count; D004305:Dose-Response Relationship, Drug; D005260:Female; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology
chemical_list: D011994:Recombinant Proteins; D007371:Interferon-gamma