Understanding the heterogeneity of natural killer cells at the maternal-fetal interface: implications for pregnancy health and disease

Natural killer (NK) cells are the most abundant leukocytes located at the maternal-fetal interface; they respond to pregnancy-related hormones and play a pivotal role in maintaining the homeostatic micro-environment during pregnancy. However, due to the high heterogeneity of NK cell subsets, their categorization has been controversial. Here, we review previous studies on uterine NK cell subsets, including the classic categorization based on surface markers, functional molecules, and developmental stages, as well as single-cell RNA sequencing-based clustering approaches. In addition, we summarize the potential pathways by which endometrial NK cells differentiate into decidual NK (dNK) cells, as well as the differentiation pathways of various dNK subsets. Finally, we compared the alterations in the NK cell subsets in various pregnancy-associated diseases, emphasizing the possible contribution of specific subsets to the development of the disease.