Trophoblast‐derived CXCL12 promotes CD56 bright CD82 ‐ CD29 + NK cell enrichment in the decidua

PROBLEM: Decidual natural killer (dNK) cells play key roles in maternal-fetal immune regulation, trophoblast invasion, and vascular remodeling, and most dNK cell populations are CD56(bright) CD16(-) NK cells. However, the enrichment and redistribution of dNK cells in the local decidua have not been clarified yet. METHOD OF STUDY: A total of 45 women with normal pregnancies and 8 unexplained recurrent spontaneous abortion (RSA) patients were included. We isolated primary human dNK (n = 53) and peripheral blood NK (pNK) cells (n = 5) from specimen and analyzed CD56, CD82, and CD29 by flow cytometry (FCM). We assessed their adhesion ability by cell counts of NK cells adhered to decidual stromal cells (DSCs) in a co-culture system. RESULTS: We found that RSA patients had more CD56(dim) dNK cells with lower CD82 and higher CD29 than women with normal pregnancies. There were negative correlations of CD82 to CD29 on CD56(dim) and CD56(+) dNK cells. In normal pregnancies, dNK cells had lower CD82 and higher CD29 expression with a stronger adhesion ability than pNK cells. Blocking CD82 on dNK cells increased the adhesive ability and CD29 expression, while blocking CD29 decreased the adhesive ability. Co-culturing dNK cells with trophoblast cells decreased CD82 expression and increased the adhesive ability of dNK cells and the percentage of CD56(bright) NK cells, while blocking trophoblast-derived CXCL12 increased CD82 expression, decreased CD29 expression, and impaired the adhesive ability of NK cells. CONCLUSION: Trophoblast cells enhance the adhesive ability of NK cells to DSCs via the CXCL12/CD82/CD29 signaling pathway and contribute to CD56(bright) NK cell enrichment in the uterus.