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.
Highlights
Immunologists have been captivated by the link between mother and fetus
Trophoblast cells have been discovered to express ligands for key natural killer (NK) receptor activators. These receptor/ligand interactions mediate the molecular contact between decidual natural killer (dNK) cells and trophoblasts, and activated dNK cells release VEGF and stromal cell derived factor-1 (SDF-1) that are important in angiogenesis [36] (Figure 2). dNK cells secrete angiogenic factors such as VEGF and angiopoietin-2, as well as cytokines and growth factors such as TNF-γ, IL-10, GM-CSF, placental growth factor (PlGF), IL-1, TGF-1, Colony stimulating factor1 (CSF-1), leukemia inhibiting factor (LIF), and IFN-γ during pregnancy [59]
DNK cells boost Treg cells and the creation of indoleamine 2,3-dioxygenase (IDO, a vital negative regulator of immune responses) producing monocytes, induce effector T cell apoptosis, and contribute to the development of decidua basalis of mouse [61,82,83,84] (Table 1). These findings show that dNK cells operate as messengers during pregnancy by controlling local inflammatory reactions and endurance
Summary
Immunologists have been captivated by the link between mother and fetus. Various theories have been put forward to explain this process, including the original theories of the fetus antigenic immaturity, inertness of the maternal immune system, and the presence of an anatomical barrier between the mother and the embryo All of these theories have been proven false and in the recent years, the concept of active immune crosstalk has gained popularity, which supports the idea that the immune system at the implantation site is not inhibited; rather, it is active, functional, and carefully managed [2].Recent research findings suggest that the fetal cells and the mother’s immune cells including innate lymphoid cells (ILCs), T regulatory cells, macrophages, etc., are engaged in a bidirectional immune conversation [3,4]. NK cells are a highly specialized subset of large granular lymphocytes that roughly make up about 15% of all circulating lymphocytes [9] They are the large cytotoxic innate lymphoid cells that regulate leukocyte activation and microbial infection surveillance immunologically [10,11]. This review will provide in-depth information on the role of NK cells during pregnancy and related disorders
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