Fetal and maternal immune cells exhibit tandem maturation across gestation and dysregulation in preterm birth

Rice, T. A.; Cao, Y.; Bichmann, L.; Snisky, T. S.; Singh, S.; Gu, W.; Yimlamai, D.; Radda, J. S. D.; Wang, S.; Tsang, J. S.; Megli, C.; Konnikova, L.

doi:10.1101/2025.09.20.677440

bioRxiv · 10.1101/2025.09.20.677440

Fetal and maternal immune cells exhibit tandem maturation across gestation and dysregulation in preterm birth

Rice, T. A.·Cao, Y.·Bichmann, L.·Snisky, T. S.·Singh, S.·Gu, W.·Yimlamai, D.·Radda, J. S. D.·Wang, S.·Tsang, J. S.·Megli, C.·Konnikova, L.

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Abstract

Appropriate regulation of maternal immune cells in the pregnant uterus is essential for successful pregnancy, yet the impact of immune cells in placental villi (PV) on placental health remain understudied. We enriched immune cells from term and preterm PV for transcriptomic and functional analyses. Maternal and fetal immune cells were abundant, with maternal chimerism increasing at term. Fetal lymphocytes displayed enhanced prostaglandin-D signatures, while maternal lymphocytes were enriched for antigen presentation pathways. Inflammatory cytokines and expanded maternal and fetal T cell clones peaked at term but did not induce cytotoxicity in placental organoids, whereas expanded T cells from idiopathic preterm cases impaired trophoblast growth and endocrine function ex vivo. These findings reveal significant immune chimerism within PV in both health and disease yet implicate PV T cells in idiopathic preterm birth. One Sentence SummaryFetal-maternal immune chimerism is characteristic of all placental villi, yet unchecked T cells and cytokines can hinder trophoblast growth and potentially precipitate preterm birth.

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Rice, T. A., Cao, Y., Bichmann, L., Snisky, T. S., Singh, S., Gu, W., Yimlamai, D., Radda, J. S. D., Wang, S., Tsang, J. S., Megli, C., Konnikova, L.. 2025-09-21. Fetal and maternal immune cells exhibit tandem maturation across gestation and dysregulation in preterm birth. https://doi.org/10.1101/2025.09.20.677440

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