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TGFb1 suppresses the activation of distinct dNK subpopulations in preeclampsia

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...

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Autores principales: Zhang, Jianhong, Dunk, Caroline E., Shynlova, Oksana, Caniggia, Isabella, Lye, Stephen J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355656/
https://www.ncbi.nlm.nih.gov/pubmed/30579870
http://dx.doi.org/10.1016/j.ebiom.2018.12.015
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author Zhang, Jianhong
Dunk, Caroline E.
Shynlova, Oksana
Caniggia, Isabella
Lye, Stephen J.
author_facet Zhang, Jianhong
Dunk, Caroline E.
Shynlova, Oksana
Caniggia, Isabella
Lye, Stephen J.
author_sort Zhang, Jianhong
collection PubMed
description 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.
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spelling pubmed-63556562019-02-08 TGFb1 suppresses the activation of distinct dNK subpopulations in preeclampsia Zhang, Jianhong Dunk, Caroline E. Shynlova, Oksana Caniggia, Isabella Lye, Stephen J. EBioMedicine Research paper 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. Elsevier 2018-12-19 /pmc/articles/PMC6355656/ /pubmed/30579870 http://dx.doi.org/10.1016/j.ebiom.2018.12.015 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research paper
Zhang, Jianhong
Dunk, Caroline E.
Shynlova, Oksana
Caniggia, Isabella
Lye, Stephen J.
TGFb1 suppresses the activation of distinct dNK subpopulations in preeclampsia
title TGFb1 suppresses the activation of distinct dNK subpopulations in preeclampsia
title_full TGFb1 suppresses the activation of distinct dNK subpopulations in preeclampsia
title_fullStr TGFb1 suppresses the activation of distinct dNK subpopulations in preeclampsia
title_full_unstemmed TGFb1 suppresses the activation of distinct dNK subpopulations in preeclampsia
title_short TGFb1 suppresses the activation of distinct dNK subpopulations in preeclampsia
title_sort tgfb1 suppresses the activation of distinct dnk subpopulations in preeclampsia
topic Research paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355656/
https://www.ncbi.nlm.nih.gov/pubmed/30579870
http://dx.doi.org/10.1016/j.ebiom.2018.12.015
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