Abstract
Innate lymphoid cells (ILCs) are the most abundant immune cells in the uterine mucosa both before and during pregnancy. Circumstantial evidence suggests they play important roles in regulating placental development but exactly how they contribute to the successful outcome of pregnancy is still unclear. Uterine ILCs (uILCs) include subsets of tissue-resident natural killer (NK) cells and ILCs, and until recently the phenotype and functions of uILCs were poorly defined. Determining the specific roles of each subset is intrinsically challenging because of the rapidly changing nature of the tissue both during the menstrual cycle and pregnancy. Single-cell RNA sequencing (scRNAseq) and high dimensional flow and mass cytometry approaches have recently been used to analyse uILC populations in the uterus in both humans and mice. This detailed characterisation has significantly changed our understanding of the heterogeneity within the uILC compartment. It will also enable key clinical questions to be addressed including whether specific uILC subsets are altered in infertility, miscarriage and pregnancy disorders such as foetal growth restriction and pre-eclampsia. Here, we summarise recent advances in our understanding of the phenotypic and functional diversity of uILCs in non-pregnant endometrium and first trimester decidua, and review how these cells may contribute to successful placental development.
Highlights
The endometrial lining of the uterus is a highly unusual mucosal surface
Investigating Uterine NK (uNK) functions were carried out prior to the discovery of other uILCs, which would have contaminated these preparations. Some of these questions will need to be revisited to establish the functions of different uILC subsets at each stage of the reproductive cycle
Understanding where human and mouse uILC and uNK subsets localise in the endometrium and during pregnancy will be essential to understanding their functions
Summary
The endometrial lining of the uterus is a highly unusual mucosal surface. It is a dynamic tissue that, in response to steroid hormones from the ovary, undergoes shedding, repair, extensive growth and remodelling up to 400 times between menarche and menopause (Figure 1A). These include trophoblast invasion into the decidua and the involvement of both foetal trophoblast and maternal uNK cells in spiral artery remodelling to ensure sufficient blood reaches the haemochorial placenta This suggests mice can provide a useful model to study the role of NK cells and ILCs in placental development. While this study did not investigate uterine ILCs in these women, the results suggest NK cells and other ILCs are not essential for reproduction under normal conditions, but can influence pregnancy outcome by fine-tuning placental development and foetal growth This is likely achieved by fulfilling multiple functions including regulating trophoblast invasion, and remodelling of the vasculature and decidual tissue. UILCs contribute through multiple redundant mechanisms to enhance the resilience of pregnancy to various challenges including infection of the uterine mucosa, while accommodating the invasion of semiallogenic trophoblast
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
