Abstract
The objective of this study was to investigate alterations in human first-trimester decidual immune cells (DICs) and relevant cytokines after treatment with prednisone. Decidual lymphocytes were treated with prednisone alone, cytokines alone or the combination of prednisone and cytokines. Levels of STAT3, STAT5, RORC and FOXP3 mRNA were assayed using quantitative real-time PCR, proportions of CD4+ T helper 17 (Th17) and CD4+ T regulatory (Treg) cells were measured using flow cytometry, and concentrations of interleukin (IL)-17A and IL-10 were determined using enzyme-linked immunosorbent assay. After treatment with prednisone alone, levels of STAT5 and FOXP3 mRNA were significantly higher than in untreated control cells (both P < 0.01), while levels of RORC mRNA were significantly lower than in controls (P < 0.05). Levels of STAT3 mRNA did not vary significantly with treatment. After treatment with prednisone alone, proportions of Th17/CD4+ cells and levels of IL-17A were significantly lower than in control cells, and proportions of Treg/CD4+ cells and levels of IL-10 significantly higher than in controls (all P < 0.01). Our results suggest that prednisone may improve pregnancy outcomes by restoring immunological homeostasis through up-regulation of STAT5 and FOXP3, induction of DIC differentiation into Treg cells, inhibition of DIC differentiation into Th17 cells, reduction of IL-17A secretion and induction of IL-10 secretion.
Highlights
Half of patients who suffer at least two pregnancy losses before gestational week 20 are diagnosed with unexplained recurrent spontaneous abortion (URSA) [1], which is largely associated with failure of the maternal-fetal immunological tolerance system [2]
Our results suggest that prednisone may improve pregnancy outcomes by restoring immunological homeostasis through up-regulation of STAT5 and FOXP3, induction of decidual immune cells (DICs) differentiation into T regulatory (Treg) cells, inhibition of DIC differentiation into T helper 17 (Th17) cells, reduction of IL-17A secretion and induction of IL-10 secretion
To gain further mechanistic insights, we stimulated DICs with IL-23, IL-6 and transforming growth factor-β (TGF-β) in order to induce their differentiation into Th17 cells, and we examined how prednisone affects the balance of Th17 and Treg cells in early pregnancy
Summary
Half of patients who suffer at least two pregnancy losses before gestational week 20 are diagnosed with unexplained recurrent spontaneous abortion (URSA) [1], which is largely associated with failure of the maternal-fetal immunological tolerance system [2]. This system plays a critical role in ensuring maternal tolerance of semi-allogeneic fetal antigens, but immune imbalance can induce maternal rejection of the embryo. IL-17A is involved in certain inflammatory responses and placental development processes [7] These processes in Th17 cells drive immune reactions, which when excessive may contribute to URSA. Proportions of Th17 cells in peripheral blood are higher www.impactjournals.com/oncotarget in URSA patients than in healthy pregnant women, suggesting that unbalanced activity by Th17 cells may harm maintenance of pregnancy [8]
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