Phosphorylated STAT3 inhibited the proliferation and suppression of decidual Treg cells in unexplained recurrent spontaneous abortion.

This study aimed to investigate the effects of signal transducer and activators of transcription 3 (STAT3) phosphorylation on the function of decidual regulatory T (Treg) cells in unexplained recurrent spontaneous abortion (URSA) patients and to explore the mechanism of STAT3 in URSA. Treg cells were sorted out from the decidual tissue by magnetic beads. The inhibitor Stattic was utilized to alter the phosphorylation status of STAT3 (pSTAT3) in Treg cells. The proliferation and suppression of Treg cell were detected by flow cytometry, real-time quantitative fluorescent PCR and ELISA. The factors that caused the hyperphosphorylation of Treg cells were detected. Our results showed that the proportion of pSTAT3 cells in the decidual Treg cells of URSA patients was significantly increased. pSTAT3 inhibited the proliferation of Treg cells by downregulating the expression of STAT5 and Foxp3 and increased the number of responder T cells. pSTAT3 decreased the secretion of TGF-β1 and IL-10 in Treg cells. Overexpression of pro-inflammatory cytokines IL-6 and IL-23 stimulated STAT3 phosphorylation in Treg cells. This study suggests that hyperphosphorylation of STAT3 impairs the proliferation, suppression and cytokine secretion of Treg cells, while inhibiting the phosphorylation of STAT3 restores these functions. These findings clarify the role of STAT3 in the pathogenesis of URSA and provide new ideas for the treatment of URSA.