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

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 (ROR?t), a master regulator of IL-17 producing cell development. These mutant mice (ROR?t 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 ROR?t 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.

SUBMITTER: Tome S

PROVIDER: S-EPMC6842800 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Tome Saki S Sasaki Tetsuya T Takahashi Satoru S Takei Yosuke Y

Experimental animals 20190610 4

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-cadh ...[more]

PMID: 31178537

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