Conclusions
Our findings demonstrate a unique immune-regulatory characteristic of placental enEVTs to develop immune tolerance along the placental-maternal circulation. New insights into the pathogenesis of RSA are also suggested.
Methods
In situ hybridization, immunofluorescence, ELISA and FCM assay were performed to examine TGF-β1 expression and distribution of regulatory T cells (Tregs) along the placental-maternal circulation route. The primary enEVTs, interstitial extravillous trophoblasts (iEVTs) and decidual endothelial cells (dECs) were purified by FACS, and their conditioned media were collected to treat naïve CD4+ T cells. Treg differentiation was measured by FLOW and CFSE assays.
Results
We found that enEVTs but not iEVTs or dECs actively produced TGF-β1. The primary enEVTs significantly promoted naïve CD4+ T-cell differentiation into immunosuppressive FOXP3+ Tregs, and this effect was dependent on TGF-β1. In recurrent spontaneous abortion (RSA) patients, an evidently reduced proportion of TGF-β1-producing enEVTs and their ability to educate Tregs differentiation were observed. Conclusions: Our findings demonstrate a unique immune-regulatory characteristic of placental enEVTs to develop immune tolerance along the placental-maternal circulation. New insights into the pathogenesis of RSA are also suggested.