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To serve and to protect: the role of decidual innate immune cells on human pregnancy

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Abstract

The maternal–fetal interface undergoes dynamic changes that promote successful development of the embryo/fetal allograft during pregnancy. This immune privilege of the conceptus is mediated through local and systemic cellular responses. In species in which endometrial decidualization accompanies pregnancy, unique immune cell niches are found. Many studies have addressed the enigmatic roles of uterine (u)NK cells as killers and helpers because they are frequently found in the uterine lining and decidua of normal and pathological pregnancies. Accumulating evidence indicates that uNK cells are induced and transformed by sensing signals within their microenvironment to both protect the mother from the fetal allograft and support the fetus during its development. Here, we review the mechanisms that modulate these functions of uNK cells during pregnancy. We suggest that uNK cells must be tightly regulated in order to serve these two roles and support a healthy pregnancy.

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Abbreviations

ADAM:

A disintegrin and metalloprotease

DC:

Dendritic cells

EVT:

Extravillous trophoblast cells

HLA:

Human leukocyte antigen

IFNG:

Interferon gamma

ILCs:

Innate lymphoid cells

KIRs:

Killer cell immunoglobulin-like receptors

MHC:

Major histocompatibility complex

NK cells:

Natural killer cells

PAS:

Periodic-acid–Schiff staining

pNK cells:

Peripheral blood NK cells

SA:

Spiral artery

Treg cells:

Regulatory T cells

TGFB:

Transforming growth factor beta

uNK cells:

Uterine natural killer cells

VEGF:

Vascular endothelial growth factor

VSMC:

Vascular smooth muscle cells

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Acknowledgments

This study was supported by awards from the Canadian Institutes of Health Research (SJL) and Natural Sciences and Engineering Research Council of Canada (BAC). We thank Dr. Oksana Shynlova (University of Toronto and Mount Sinai Hospital, Toronto) for critical review of our manuscript.

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Authors and Affiliations

  1. Research Centre for Women’s and Infants’ Health, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde St., Toronto, ON, M5T 3H7, Canada

    Jianhong Zhang, Caroline Dunk & Stephen J. Lye

  2. Department of Obstetrics & Gynaecology, University of Toronto, Toronto, ON, Canada

    Caroline Dunk & Stephen J. Lye

  3. Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, Canada

    Anne B. Croy

  4. Department of Physiology, University of Toronto, Toronto, ON, Canada

    Stephen J. Lye

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  1. Jianhong Zhang
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  2. Caroline Dunk
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Correspondence to Jianhong Zhang.

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Zhang, J., Dunk, C., Croy, A.B. et al. To serve and to protect: the role of decidual innate immune cells on human pregnancy. Cell Tissue Res 363, 249–265 (2016). https://doi.org/10.1007/s00441-015-2315-4

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