Bidirectional regulation between 1st trimester HTR8/SVneo trophoblast cells and in vitro differentiated Th17/Treg cells suggest a fetal-maternal regulatory loop in human pregnancy

American Journal of Reproductive Immunology : AJRI
Song-Cun WangDa-Jin Li

Abstract

During normal pregnancy, delicate crosstalk is established between fetus-derived trophoblasts and maternal immune cells to ensure maternal-fetal tolerance and successful placentation. Dysfunction in these interactions has been highly linked to certain pregnancy complications. Naïve CD4+ T cells were cultivated with or without 1st trimester derived trophoblast cell line HTR8/SVneo cells in the absence or presence of T helper 17 (Th17) or regulatory (Treg)cell-inducing differentiation conditions. After 5 days of co-culture, HTR8/SVneo cells and CD4+ T cells were harvested and analyzed using flow cytometry. CD4+ T cells exposed to HTR8/SVneo cells showed enhanced induction of CD4+ Foxp3+ Treg cells with strong expression of TGF-β1 and inhibitory molecules (cytotoxic T lymphocyte-associated protein-4 [CTLA-4], T-cell immunoglobulin mucin-3 [Tim-3], and programmed cell death-1 [PD-1]). Though not effecting Th17 differentiation, exposure to HTR8/SVneo cells promoted increased expression of proliferative and apoptotic markers on Th17 cells. Co-culture with Th0 cells, or differentiated Th17 or Treg cells, down-regulated Caspase-3 and MMP-9 (but not MMP-2) expression in HTR8/SVneo cells, while promoting Ki67 expression. HTR8/SVneo cells...Continue Reading

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Citations

Jan 11, 2020·Frontiers in Immunology·Anne Schumacher, Ana C Zenclussen
Jan 29, 2021·Journal of Personalized Medicine·Cristina PanisiVassilios Fanos
Dec 18, 2020·Frontiers in Immunology·Gabriel Mayoral AndradeEduardo Pérez-Campos

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Methods Mentioned

BETA
density gradient centrifugation
flow cytometry
PMA
RSA
ELISA

Software Mentioned

FlowJo
GraphPad Prism

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