Elevated maternal retinoic acid-related orphan receptor-γt enhances the effect of polyinosinic-polycytidylic acid in inducing fetal loss

母体视黄酸相关孤儿受体γt升高增强聚肌苷酸-聚胞苷酸诱发胎儿丢失的作用

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作者:Saki Tome, Tetsuya Sasaki, Satoru Takahashi, Yosuke Takei

Abstract

T helper 17 (Th17) cells have been suggested to play a crucial role in various complications during pregnancy by participating in maternal immune activation (MIA). To test a possible role for Th17 cells in MIA-mediated abortion, we analyzed transgenic mice overexpressing retinoic acid receptor-related orphan receptor gamma-t (RORγt), a master regulator of IL-17 producing cell development. These mutant mice (RORγt Tg mice) exhibited a constitutive upregulation of serum IL-17A and decreased E-cadherin expression in cell-cell junctions of placental tissues. Abortion after the administration of a viral-mimicking synthetic double-stranded RNA polyinosinic-polycytidylic acid was more frequent in RORγt Tg mice than wild-type mice. These results suggest that excessive Th17 cell activity alters immune responsiveness and increases the rate of abortion during gestation.

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