Role of Immunoregulatory Cytokine IL-15 in the Endometrium
Within the endometrial environment, which is tightly controlled by ovarian hormones, cells of the immune system play an important role in the regulation of processes that must happen in preparation for embryo implantation and placental growth. Immune cells are numerous in the endometrium; they include lymphocytes, macrophages, dendritic cells, and neutrophils. NK cells represent the most abundant and dynamic population of immune cells in the endometrium, as their number gradually increases with the progression of the menstrual cycle and remains exclusively high in decidualized stroma when pregnancy occurs. A key cytokine responsible for NK cell proliferation, survival, and functional activity is IL-15. The endometrium is among the tissues with a high IL-15 mRNA expression. The expression of IL-15 in the endometrium is low in the proliferative phase and peaks during the secretory phase. Main producers of IL-15 in the endometrium are stromal cells, which upregulate IL-15 production upon the influence of progesterone and differentiation into decidual cells. Endometrial stromal cells also express IL-15Rα; this allows them to trans-present the IL-15 to the neighboring NK cells. Prolonged stimulation of NK cells by the membrane-bound IL15/IL15Rα complex is known to mediate a metabolic reprogramming in NK cells and increase their effector functions such as degranulation. This feature of NK cells is important for clearance of senescent endometrial cells which drive a transient inflammatory reaction specific for receptive endometrium. Overexpression of IL-15 could have a detrimental effect on pregnancy development due to excessive activation of uterine NK cells. Thus, IL-15 production in endometrium has to be tightly regulated to achieve an optimal balance in tuning uterine NK cell activity toward supporting embryo implantation and placental development.
KeywordsEndometrium IL-15 NK cells Cytokine IL-15Rα
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