Immunoregulation of PD-1/PD-L1 Inhibitory Pathway on Fetomaternal Tolerance in abortion Triggered by thyroid autoimmunity
Abstract Background: TAI in euthyroid pregnant women is associated with miscarriage. Studies have shown that the PD-1/PD-L1 signaling pathway plays an important role in maternal-fetal tolerance by promoting Treg cells development and inhibition of Th17 cells responses, whereby it is essential for normal pregnancy maintenance. However, whether the PD-1/PD-L1 pathway leads to a Treg/Th17 imbalance has not been fully investigated in TAI. Methods: TAI fetal loss model was established by thyroglobulin (mTg) immunized CBA/J female mice. The frequencies of splenic Th17, Treg, PD-1 and PD-L1 were tested by flow cytometry. IL-17, Foxp3, RORγt, PD-1 and PD-L1 mRNA levels were tested by real-time PCR. Results: Compared with the control group, the number of CD4 + CD25 + Foxp3 + T lymphocyte in the placenta and spleen were significantly reduced (P<0.05) in the experimental group (mTg group), CD4 + IL-17 + T-cell subsets and expression of RORγt and IL-17 mRNA in the placenta were increased (P<0.05), the ratio of Treg/IL-17 in the placenta and spleen was decreased (P<0.05). The expression of PD-1 and PD-L1 in mice immunized with mTg in CD4 + T group decreased the subsetof cells in the placenta and spleen including Tregs. Conclusions: The role of PD-1/PD-L1 pathway in an isolated thyroglobulin antibodies (TgAb) positive mouse abortion model is that it may lead to a peripheral Treg/Th17 imbalance and the maternal-fetal tolerance balance breakdown, which may ultimately result in fetal loss.