mRNA Expression of FoxP3 and IL-10 in Deciduas from Patients with Unexplained Early Recurrent Miscarriage

Introduction Suppressive mechanisms at the fetal-maternal interface depend on the pool of regulatory T cells within the CD4+T subset, including CD25highFoxP3+T cells (Tregs) and IL-10-producing type 1 regulatory cells (Tr1). IL-10 plays a beneficial role in normal pregnancy, acting directly on Tregs to maintain Foxp3 expression and suppressive capacity. In contrast, diminished endometrial Foxp3 mRNA expression and decreased production of IL-10 are associated with unexplained early Recurrent Miscarriage (RM). Aim of this work is to evaluate the mRNA expression of FoxP3 and IL-10 in deciduas from patients with RM compared with the same tissues from women who underwent Elective Abortion (EA). Methods We collected first-trimester decidual tissue samples from 30 patients (20 with RM and 10 who underwent EA), age- and gestational age-matched. Total RNA was isolated from tissues of both subject groups for PCR-Real Time analysis of FoxP3 and IL-10, using β-actin as endogenous control. The results were expressed as means ± SD of analyzed markers respect to endogenous control. Results FoxP3 and IL-10 mRNA levels were significantly lower in decidual tissue samples of patients with RM respect to patients who underwent EA (for FoxP3: 0.43 ± 0.06 vs 2.1 ± 0.5; for IL-10: 0.34 ± 0.03 vs 1,3 ± 0.2). Conclusions In decidua of RM respect to EA patients, the significantly diminished FoxP3 mRNA levels could account for a paucity of Tregs and, together with IL-10 mRNA lower expression, lead to reduction of the immunosuppressive functions. The suppressive ability of regulatory T cells occurs through several mechanisms. Suppression by Tregs primarily requires cell-cell contact whereas Tr1 act mainly by the release of IL-10. Our results allow us to hypothesize that the first suppressive mechanism may fail for the small number of FoxP3+ cells. The decreased IL-10 production could depend, at least in part, by reduced presence or function of Tr1, which exert their immunosuppressive activity mainly through this cytokine. This might alter the decidual immune homeostasis, causing susceptibility to pregnancy loss.