Trophoblast-Derived CXCL16 Decreased Granzyme B Production of Decidual gamma delta T Cells and Promoted Bcl-xL Expression of Trophoblasts

摘要

Background: Decidual gamma delta T cells are known to regulate the function of trophoblasts at the maternal-fetal interface; however, little is known about the molecular mechanisms of cross talk between trophoblast cells and decidual gamma delta T cells. Methods: Expression of chemokine C-X-C motif ligand 6 (CXCL16) and its receptor CXCR6 was evaluated in first-trimester human villus and decidual tissues by immunohistochemistry. gamma delta T cells were isolated from first-trimester human deciduae and cocultured with JEG3 trophoblast cells. Cell proliferation and apoptosis-related molecules, together with cytotoxicity factor and cytokine production, were measured by flow cytometry analysis. Results: Expression of CXCL16 and CXCR6 was reduced at the maternal-fetal interface in patients who experienced unexplained recurrent spontaneous abortion as compared to healthy pregnancy women. With the administration of pregnancy-related hormones or coculture with JEG3 cells, CXCR6 expression was upregulated on decidual gamma delta T cells. CXCL16 derived from JEG3 cells caused a decrease in granzyme B production of decidual gamma delta T cells. In addition, decidual gamma delta T cells educated by JEG3-derived CXCL16 upregulated the expression of Bcl-xL in JEG3 cells. Conclusion: This study suggested that the CXCL16/CXCR6 axis may contribute to maintaining normal pregnancy by reducing the secretion of cytotoxic factor granzyme B of decidual gamma delta T cells and promoting the expression of antiapoptotic marker Bcl-xL of trophoblasts.