title: Trophoblasts regulate natural killer cells via control of interleukin-15 receptor signaling.
abstract: Trophoblasts 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.
  
  
  
  Natural 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.
  
  
  
  Natural 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-γ were also downregulated.
  
  
  
  Trophoblasts regulate human NK cell functions via suppression of IL-15/IL-2 receptor expression, transcription factors, and ERK/JNK pathways.
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, Myunggok Medical Research Center, Konyang University, Daejeon, Korea.
authors.forename: Seo Y
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, Myunggok Medical Research Center, Konyang University, Daejeon, Korea.
authors.forename: Sohyun
authors.initials: S
authors.lastname: Yun
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, Myunggok Medical Research Center, Konyang University, Daejeon, Korea.
authors.forename: Byung J
authors.initials: BJ
authors.lastname: Ryu
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, Myunggok Medical Research Center, Konyang University, Daejeon, Korea.
authors.forename: Ae R
authors.initials: AR
authors.lastname: Han
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, Myunggok Medical Research Center, Konyang University, Daejeon, Korea.
authors.forename: Sung K
authors.initials: SK
authors.lastname: Lee
mesh_terms: D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D048670:MAP Kinase Kinase 4 / Q000276:immunology; D053647:Receptors, Interleukin-15 / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology; D050799:STAT5 Transcription Factor / Q000276:immunology; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology; D014327:Trophoblasts / Q000276:immunology*; D000098815:T-bet Transcription Factor
chemical_list: C491199:EOMES protein, human; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D050799:STAT5 Transcription Factor; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma; D048049:Extracellular Signal-Regulated MAP Kinases; D048670:MAP Kinase Kinase 4
keywords: cytotoxicity; granzyme; interleukin-15; natural killer cell; perforin; trophoblast