IL-15 Expression at Human Endometrium and Decidua

Abstract

A large number of natural killer (NK) cells appear in human uterine mucosa during the secretory phase and first trimester pregnancy. We investigated the expression of interleukin (IL)-15, a possible stimulator for these NK cells, in human endometrium and first trimester decidua. Semiquantitative reverse transcriptase-polymerase chain reaction revealed that IL-15 mRNA expression was stronger during the secretory phase and first trimester pregnancy than during the proliferative phase. Immunohistochemistry revealed that immunoreactivity for anti-IL-15 was higher during the secretory phase than it was during the proliferative phase. This was prominent in the perivascular stromal cells around invading spiral arteries during the mid- to late-secretory phase. In first trimester decidua, endothelial cells were also stained as strongly as stromal cells. A membrane-bound IL-15 molecule was detected on the surface of first trimester decidual cells by flow cytometry. Progesterone stimulated the release of soluble IL-15 in the supernatant of cultured decidual cells. These results suggest that IL-15 expression in human uterine mucosa corresponds to the fluctuation of uterine NK cells and that its production is hormonally controlled, especially by progesterone.

The CXCL12/CXCR4 axis is involved in the maintenance of Th2 bias at the maternal/fetal interface in early human pregnancy

“…27 DSCs are involved in a series of immune regulatory processes, such as the production of cytokines as well as antigen phagocytosis and presentation, [28][29][30] indicating that DSCs might be an important regulator on Th2 bias at the maternal/ fetal interface.…”

Variability in human semen content and its potential effects in the female reproductive tract

“…Although it remains controversial, the shift in uNK phenotype leading to tolerance may be induced by IL-15 and IL-7 [33]. Release of IL-15 from the epithelium is increased 22-fold in the subepithelial space as early 4 h post-semen exposure [34]. As mentioned previously, the combination of IL-15 and TGF-β increases T-cell switching to a T reg phenotype, further contributing to key events that initiate fetal tolerance [13].…”

Natural Killer Cell Reduction and Uteroplacental Vasculopathy

“…16,46,54 We detected an increase in interleukin-15 gene expression in the mesometrial triangles of anti-asialo GM1-treated, preeclamptic rats at the end of pregnancy. In humans, interleukin-15 is expressed by endometrial stromal cells 55 and involved in recruitment of uNK cells to the endometrium. 56 One could interpret the increase in interleukin-15 in the mesometrial triangle after NK cell reduction as a homeostatic, compensatory mechanism to replenish the uNK cell population, confirming the successful reduction of NK cells in the uterus.…”