Role of Natural Killer Cells during Pregnancy and Related Complications

Abstract

A high number of leucocytes reside in the human endometrium and are distributed differentially during the menstrual cycle and pregnancy. During early pregnancy, decidual natural killer (dNK) cells are the most common type of natural killer (NK) cells in the uterus. The increase in the number of uterine NK (uNK) cells during the mid-secretory phase of the menstrual cycle, followed by further increase of dNK cells in early pregnancy, has heightened interest in their involvement during pregnancy. Extensive research has revealed various roles of dNK cells during pregnancy including the formation of new blood vessels, migration of trophoblasts, and immunological tolerance. The present review article is focused on the significance of NK cells during pregnancy and their role in pregnancy-related diseases. The article will provide an in-depth review of cellular and molecular interactions during pregnancy and related disorders, with NK cells playing a pivotal role. Moreover, this study will help researchers to understand the physiology of normal pregnancy and related complications with respect to NK cells, so that future research work can be designed to alleviate the complications.

Keywords: decidual angiogenesis; endometrium; naturalkiller cells; preeclampsia; pregnancy.

Figure 1

Cellular stages of Natural Killer (NK) cell development: (A) murine; (B) humans. In both cases the NK cells develop in the bone marrow from the common progenitor hematopoietic stem cells (HSC) and pass through the five different cellular stages to become a mature NK (mNK) cell, each of which is characterized by the different surface markers. CLP: Common lymphoid progenitor cells. NKP: Natural killer progenitor cells.

Figure 2

Interaction of trophoblast and decidual NK (dNK) cells at the maternal-fetal border. The interactions between the trophoblast and dNK cells are mediated by multiple interactions of receptor ligands at the interface between the mother and the fetus. This leads to activation of dNK cells, and the activated dNK cells release the cytokines and chemokines that play vital role placental development by mediating trophoblast invasion, angiogenesis and remodeling of placental tissues/spiral arteries. VEGF: Vascular endothelial growth factor; IL-8: Interleukin-8; IP-10: Interferon inducible protein-10; SDF-1: Stromal cell derived factor-1; CD-69: Cluster of Differentiation-69; CD-9: Cluster of Differentiaton-9; KIRs: Killer Ig-like receptors; NCRs: Natural cytotoxicity receptors; NKG2D: Natural killer group 2D; DNAM-1: DNAX accessory molecule.