The experimental research of pregnancy immune tolerance induced by FTY720 via blocking S1P signal transduction pathway.

Objective: To investigate the effects of pregnancy immune tolerance induced by FTY720 via blocking S1P signal transduction pathway.

Methods: Immunohistochemistry was used to detect the expression of S1P in the decidua of pregnant rats. We have constructed S1P gene small interfering RNA (siRNA) lentiviral vector and overexpression S1P gene lentiviral vector and they are transferred into dendritic cell (DC), then observing the effect of adoptive transferring of FTY720 on the embryo loss rate of spontaneous abortion mouse model after transferring this two kinds of lentiviral vectors.

Results: (1) FTY720 had no significant effect on the embryo loss rate of the normal pregnant rats; (2) Adoptive transferring of FTY720 can significantly reduce the embryo loss rate of the spontaneous abortion mouse model. The expression of S1P in the decidua of spontaneous abortion mouse model was lower than that of normal pregnant rat (P < 0.05). (3) After transferring of S1P-siRNA lentiviral vector transfected DC, FTY720 could mild reduce the embryo loss rate of abortion mouse model (embryo loss rate was 11.5%) ( P < 0.05). However, the effect is far less than that of before adoptive transferring of S1P-siRNA lentivirus transfected DC. After the transferring of the overexpression of S1P gene lentiviral vector transfected DC, FTY720 can significantly reduce the rate of embryo loss in the spontaneous abortion mouse model (embryo loss rate decreased to 1.95%) ( P < 0.01). The effect was more obvious than that of no transfecting S1P gene lentiviral vector transfected DC.

Conclusion: FTY720 is secured in inducing immune tolerance during pregnancy by blocking the S1P signaling pathway.