Expression of NKp46 and other activating inhibitory receptors on uterine endometrial NK cells in females with various reproductive failures: A review.

Background: Uterine endometrial natural killer (uNK) cells represent major leukocytes in the mid-secretory phase of the cell cycle, and their number is further increased during early pregnancy. The activating and inhibitory receptors expressed on their surface mediate various functions of uNK cells, such as cytotoxicity, cytokine production, spiral artery remodeling, and self-recognition. Methods: This study reviewed the most recent information (PubMed database, 175 articles included) regarding the activating and inhibitory receptors on uNK cells in human females with healthy pregnancies and the evidence indicating their significance in various reproductive failures. Main Findings: Numerous studies have indicated that the natural cytotoxic receptors, killer cell immunoglobulin-like receptors, and C-type lectin receptors, particularly those expressed on uNK cells, play crucial roles in successful pregnancy. Conclusion: As studies on human uNK cells are limited owing to the low availability of fertile samples, and the extrapolation of animal models has certain limitations, the in vivo role of uNK cells has not yet been fully elucidated. However, immunotherapies focusing on modulating uNK cell function have been controversial in terms of pregnancy outcomes. Further research is required to elucidate the role of uNK cells in reproduction.