Research ArticleMATERNAL-FETAL IMMUNOLOGY

Extrathymic Aire-expressing cells support maternal-fetal tolerance

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Science Immunology  16 Jul 2021:
Vol. 6, Issue 61, eabf1968
DOI: 10.1126/sciimmunol.abf1968

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Aire-expressing cells defend the fetus

The normal maternal immune system adapts to pregnancy by learning to tolerate both allogeneic paternal and pregnancy-associated antigens expressed by the fetus and placenta. Gillis-Buck et al. investigated the contribution of cells expressing the autoimmune regulator (Aire) gene to maintaining fetal health using a mouse model in which Aire-expressing cells were deleted during early pregnancy. Ablation of Aire-expressing cells did not impair fetal implantation but resulted in intrauterine fetal growth restriction during both allogeneic and syngeneic pregnancies associated with increased activation of effector T cells. Selective deletion of extrathymic Aire-expressing cells (eTACs) while preserving Aire-expressing thymic epithelial cells revealed that eTACs are required for maintaining tolerance and fetal health. These findings demonstrate an unanticipated role for eTACs as guardians of fetal health during pregnancy.

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