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Biology and pathology of the uterine microenvironment and its natural killer cells.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Wang, Fuyan 
Qualls, Anita Ellen 
Marques-Fernandez, Laia 

Abstract

Tissues are the new frontier of discoveries in immunology. Cells of the immune system are an integral part of tissue physiology and immunity. Determining how immune cells inhabit, housekeep, and defend gut, lung, brain, liver, uterus, and other organs helps revealing the intimate details of tissue physiology and may offer new therapeutic targets to treat pathologies. The uterine microenvironment modulates the development and function of innate lymphoid cells [ILC, largely represented by natural killer (NK) cells], macrophages, T cells, and dendritic cells. These immune cells, in turn, contribute to tissue homeostasis. Regulated by ovarian hormones, the human uterine mucosa (endometrium) undergoes ~400 monthly cycles of breakdown and regeneration from menarche to menopause, with its fibroblasts, glands, blood vessels, and immune cells remodeling the tissue into the transient decidua. Even more transformative changes occur upon blastocyst implantation. Before the placenta is formed, the endometrial glands feed the embryo by histiotrophic nutrition while the uterine spiral arteries are stripped of their endothelial layer and smooth muscle actin. This arterial remodeling is carried out by invading fetal trophoblast and maternal immune cells, chiefly uterine NK (uNK) cells, which also assist fetal growth. The transformed arteries no longer respond to maternal stimuli and meet the increasing demands of the growing fetus. This review focuses on how the everchanging uterine microenvironment affects uNK cells and how uNK cells regulate homeostasis of the decidua, placenta development, and fetal growth. Determining these pathways will help understand the causes of major pregnancy complications.

Description

Keywords

Decidua, Natural killer cells, Pregnancy, Uterine microenvironment, uNK, Biology, Decidua, Female, Humans, Immunity, Innate, Killer Cells, Natural, Pregnancy, Uterus

Journal Title

Cell Mol Immunol

Conference Name

Journal ISSN

1672-7681
2042-0226

Volume Title

18

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (200841/Z/16/Z)