Altered Expression of CXCL16/CXCR6 and Its Correlation with Decidual Macrophage Polarization in Preeclampsia

The CXCL16/CXCR6 signaling pathway is implicated in macrophage polarization. The correlation between CXCL16 and CXCR6 expressions in decidual tissues from patients with preeclampsia (PE) and macrophage polarization remains unexplored. This study aimed to investigate the correlation between the chemokine axis CXCL16/CXCR6 and macrophage polarization at the maternal-fetal interface in PE.

In this study, macrophage polarization status in the decidua was assessed using Western blotting (WB), immunohistochemistry (IHC), and immunofluorescence (IF) staining. For quantitative characterization, primary decidual macrophages were isolated and subjected to flow cytometry analysis to further evaluate macrophage polarization. Expression of CXCL16 and CXCR6 in decidual tissues was evaluated by WB and IHC. Additionally, the expressions of CXCL16 and CXCR6 in decidual macrophages were assessed by immunofluorescence double staining.

IHC and WB demonstrated a significant upregulation of CD86 (P < 0.05), alongside a downregulation of CXCL16, CXCR6, and CD206 (P < 0.01) in PE decidual tissues. IF double staining revealed an increased abundance of CD68⁺CD80⁺/CD86⁺ cells in the decidua of patients with PE, while CD68⁺CD163⁺/CD206⁺ and CD68⁺CXCL16⁺/CXCR6⁺ cells was decreased. Flow cytometry analysis of primary decidual macrophages isolated from PE patients confirmed an increase in the proportions of CD68⁺CD80⁺ (P < 0.01) and CD68⁺CD86⁺ (P < 0.0001), and a marked decrease in CD68⁺CD163⁺ (P< 0.001) and CD68⁺CD206⁺ (P < 0.0001). These results indicate dysregulated decidual macrophage polarization in PE, characterized by an M1 bias that may be mediated by impaired CXCL16/CXCR6 signaling at the maternal-fetal interface.