The novel role of activating receptor KIR2DS5 in preeclampsia

• Published in: International immunopharmacology Vol. 125; no. Pt A; p. 111087
• Main Authors: Wei, Xiaoqi, Yang, Xiuhua
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2023
• Subjects: Cell Line; Decidua - metabolism; Female; GM-CSF; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Humans; Killer Cells, Natural - metabolism; KIR2DS5; Placenta; Pre-Eclampsia - genetics; Pre-Eclampsia - metabolism; Preeclampsia; Pregnancy; Receptors, KIR - metabolism; Pregnancy; KIR2DS5; Placenta; GM-CSF; Preeclampsia
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2023.111087

•The mRNA and protein expressions of KIR2DS5 were evidently lower in PE deciduae.•KIR2DS5 silencing reduced the motility of trophoblasts and promoted cell apoptosis in trophoblast-dNK co-culture systems.•There was a positive link between KIR2DS5 and GM-CSF in trophoblast-dNK cells.•KIR2DS5 regulated the level of GM-CSF via the JAK2/STAT5 signaling pathway.•Decreased KIR2DS5 at the uteroplacental interface may contribute to the etiology of PE. Preeclampsia (PE) is a serious complication of pregnancy. Decidual natural killer (dNK) cells were reported to participate in the remodeling of spiral arteries through producing a group of cytokines, including granulocyte–macrophage colony stimulating factor (GM-CSF). KIR2DS5 is an activating receptor of NK cells that specifically recognizes HLA-C2 on trophoblasts. Currently, there are no reports regarding the precise mechanism of KIR2DS5 in PE. This study included 30 PE patients and 30 healthy pregnant women. We found that the expressions of KIR2DS5 were significantly lower in PE deciduae compared to those of healthy pregnancies. By transfecting knockdown and overexpression lentivirus vectors of KIR2DS5 into dNK cells isolated from deciduae of early pregnancy, we altered the KIR2DS5 expression level in dNK cells. Then, these dNK cells and trophoblast cell lines were co-cultured as trophoblast-dNK cells. In the trophoblast-dNK cells, we examined the influence of KIR2DS5 on the biological manifestations of trophoblasts. As anticipated, overexpression of KIR2DS5 could facilitate cell proliferation, migration, and invasion. Furthermore, increased expression of KIR2DS5 inhibited cell apoptosis and enhanced the progression of cells from theG1 to theS stage. Further mechanistic study demonstrated a positive relationship between KIR2DS5 and GM-CSF in trophoblast-dNK cells. Accordingly, our observations indicated that a decrease in KIR2DS5 could reduce the expression of GM-CSF via the JAK2/STAT5 pathway, resulting in the failure of the activated signal to be transmitted to dNK cells and ultimately leading to the occurrence of PE. KIR2DS5 may be a new contributor for the prediction and diagnosis of PE.