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EBioMedicine. 2019 Jan;39:531-539. doi: 10.1016/j.ebiom.2018.12.015. Epub 2018 Dec 19.

TGFb1 suppresses the activation of distinct dNK subpopulations in preeclampsia.

Author information

1
Research Centre for Women's and Infants' Health, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto M5T 3H7, Canada.
2
Research Centre for Women's and Infants' Health, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto M5T 3H7, Canada; Department of Obstetrics & Gynecology, University of Toronto, Toronto M5G 1L4, Canada.
3
Research Centre for Women's and Infants' Health, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto M5T 3H7, Canada; Department of Obstetrics & Gynecology, University of Toronto, Toronto M5G 1L4, Canada; Department of Physiology, University of Toronto, Toronto M5G 1L4, Canada. Electronic address: LYE@lunenfeld.ca.

Abstract

BACKGROUND:

Decidual natural killer (dNK) cells are the predominant lymphocytes accumulated at the maternal-fetal interface. Regulatory mechanism of dNK cells in preeclampsia, a gestational complication characterized by high blood pressure and increased proteinuria occurring after 20 weeks pregnancy, is not completely understood.

METHODS:

Multi-parameter flow cytometry is applied to investigate the phenotype and function of dNK cells freshly isolated from decidual samples or conditionally cultured by TGFb stimulation.

FINDINGS:

In preeclampsia, we documented elevated numbers of CD56+ CD3- dNK cells in close proximity to Foxp3+ regulatory T (Treg) cells within the decidua. In vitro experiments using dNK cells from early gestation showed that dNK activation (IFNG, IL-8 and CD107a) can be downregulated by Treg cells. The expression of these markers by dNK cells was significantly lower in preeclampsia. We also observed a positive correlation between the expression of dNK activation receptors (NKp30 and NKG2D) and the expression of IFNG in specific dNK subsets. TGFb levels are increased in the decidua of preeclamptic pregnancies. We analyzed co-expression of activation (IFNG/IL-8/CD107a) and angiogenic (VEGF) markers in dNK cells. TGFb treatment reduced while blockade of TGFb increased co-expression of these markers.

INTERPRETATION:

Our findings suggest that elevated decidual TGFb1 supresses the activation of specific subsets of dNK which in turn contributes to the uteroplacental pathology associated with the onset of preeclampsia.

KEYWORDS:

IFN-gamma; Preeclampsia; TGF-beta; Treg cells; dNK cells

PMID:
30579870
PMCID:
PMC6355656
DOI:
10.1016/j.ebiom.2018.12.015
[Indexed for MEDLINE]
Free PMC Article

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