Abstract
NK cells are lymphocytes involved in the innate and adaptative immune response. These cells are located in peripheral blood and tissues with ample functions, from immune vigilant to tolerogenic reactions. In the endometrium, NK cell populations vary depending on age, hormones, and inflammation. When pregnancy occurs, tissue-resident NK cells and conventional NK cells are recruited to protect the fetus, a tolerogenic response. On the contrary, in the inflamed endometrium, various inflammatory cells down-regulate NK tolerance and impair embryo implantation. Therefore, NK cells’ pharmacological modulation is difficult to achieve. Several strategies have been used, from progesterone, lipid emulsions to steroids; the success has not been as expected. However, new therapeutic approaches have been proposed to decrease the endometrial inflammatory burden and increase pregnancy success based on understanding NK cell physiology.
Highlights
Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Palacky University, Abstract: Natural killer cells (NK) cells are lymphocytes involved in the innate and adaptative immune response
NK cells can be transformed from one type to another depending on tissue milieu, cytokine or receptor stimulation, or pharmacologic therapy [1,2]
Chemokines secreted by the tissue may recruit tissue independent NK cells from the bloodstream, and once they arrive at their destination, their cell functions may be modulated by tissue milieu [10,11,12]
Summary
Progesterone is essential in reproduction and pregnancy maintenance. The hormone induces the transcription and secretion of progesterone-induced blocking factor (PIBF) [14,15]. Fetal expression of MHC-I and its recognition by KIR receptors on NK cells, along with NKG2A/CD94, are critical for dNK cells (Table 1). KIR antigen expression in dNK1 cells correlates with granzyme B granule content in the cells suggesting that these cells are more prone to be cytotoxic These results indicate that KIR receptors control fetal development and could be involved in eliminating abnormal trophoblasts [24]. DNK cells, usually tolerogenic, have a higher cytotoxic response against K562 than those of the first trimester [22,23] This effect may be due to an impaired inhibitory response due to a downregulated expression of inhibitory receptors recognizing HLA-C antigens or HLA E and G as cNK cells [22,23]. The response is dependent upon the production of IFN γ and the downregulation of KIR inhibitory receptors
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