Trophoblasts regulate natural killer cells via control of interleukin-15 receptor signaling

ProblemTrophoblasts are known to decrease natural killer (NK) cell cytotoxicity. However, little is known about the interaction between trophoblasts and NK cells during pregnancy. Interleukin-15 (IL-15) is essential for priming NK cells and maximizing their effector functions. We investigated whether trophoblasts regulate NK cell activation via IL-15/IL-2 receptor and its signaling pathways. Method of studyNatural killer-92 cells were primed with human first-trimester trophoblast cells (Sw.71) conditioned medium (CM) and co-cultured with K562 cells. Flow cytometry, Western blot analysis, and real-time PCR were performed to assess NK cell cytotoxicity, IL-15/IL-2 receptor expression, phosphorylation of STAT5 and MAPKs, and mRNA expression of IL-15-related genes. ResultsNatural killer-92 cells incubated with Sw.71 CM showed reduced cytotoxicity and IL-15-mediated proliferation, and expression of IL-15/IL-2 receptor subunits. STAT5 phosphorylation, EOMES and T-bet mRNA expressions, and ERK/JNK pathways of NK 92 cells were suppressed by Sw.71 CM. Productions of perforin, granzyme B, and IFN- were also downregulated. ConclusionTrophoblasts regulate human NK cell functions via suppression of IL-15/IL-2 receptor expression, transcription factors, and ERK/JNK pathways.