CD4(+)CD25(+)Foxp3(+) regulatory T cells regulate immune balance in unexplained recurrent spontaneous abortion via the Toll-like receptor 4/nuclear factor-κB pathway

OBJECTIVE: The present study aimed to evaluate the effects of cluster of differentiation (CD)4(+)CD25(+) forkhead box p3 (Foxp3)(+) regulatory T cells (Tregs) on unexplained recurrent spontaneous abortion (URSA) and the associated mechanisms. METHODS: The proportion of CD4(+)CD25(+)Foxp3(+) Tregs and inflammatory cytokine concentrations in the peripheral blood of women with URSA were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. CBA/JxDBA/2J mating was used to establish an abortion-prone mouse model and the model mice were treated with the Toll-like receptor 4 (TLR4) antagonist E5564 and the TLR4 agonist lipopolysaccharide. RESULTS: The proportion of CD4(+)CD25(+)Foxp3(+) Tregs was decreased and the inflammatory response was increased in women with URSA. In the abortion-prone mouse model, E5564 significantly increased the proportion of CD4(+)CD25(+)Foxp3(+) Tregs, decreased the inflammatory response, and increased Foxp3 mRNA and protein expression. Lipopolysaccharide had adverse effects on the abortion-prone model. CONCLUSIONS: These data suggest that CD4(+)CD25(+)Foxp3(+) Tregs regulate immune homeostasis in URSA via the TLR4/nuclear factor-κB pathway, and that the TLR4 antagonist E5564 may be a novel and potential drug for treating URSA.