Trophoblast-derived CXCL12 promotes CD56bright CD82- CD29+ NK cell enrichment in the decidua

Abstract

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.

Keywords: CD29; CD82; CXC12; NK; abortion; adhesion; decidua; trophoblasts.