The sphingosine 1-phosphate receptor agonist FTY720 interfered the distribution of dendritic cell and induced the maternal-fetal immune tolerance.

OBJECTIVE

The aim of this study was to investigate the effect of FTY720, an agonist of the sphingosine 1-phosphate (S1P) receptor, on the embryo loss rate in mice of spontaneous abortion model and the underlying mechanism.

METHODS

The effect of intraperitoneal injection of FTY720 on the embryo loss rate in mice of spontaneous abortion model was observed. The expression of S1PR on the dendritic cell (DC) surface was detected by reverse transcription polymerase chain reaction. The quantity and maturation of DCs in peripheral blood and local tissues of pregnant mice, and the expression of CCL19 as well as its receptor C-C chemokine receptor 7 (CCR7) were detected by flow cytometry and immunohistochemistry. Chemotaxis assay was performed to verify the effect of FTY720 on the chemotaxis of DCs.

RESULTS

(1) FTY720 had no significant effect on the embryo loss rate in normal pregnant rats. In contrast, adoptive transferring of FTY720 significantly reduced the embryo loss rate of the spontaneous abortion mouse model (P < 0.05). (2) S1PR was extensively expressed on DC surface. The S1P receptor agonist FTY720 reduced the expressions of DC surface chemokines and its receptor (P < 0.05), resulting in a significant reduction in the number of DCs that were chemoattracted to maternal-fetal interface flow cytometry (P < 0.05). (3) FTY720 had no significant effect on the differentiation and apoptosis rate of DCs (P > 0.05).

CONCLUSION

We hypothesized that FTY720 may reduce the number of DCs that were chemoattracted to the maternal-fetal interface by downregulating the expression of CCR7, which ultimately induces maternal-fetal immune tolerance.