Treg/Th17 Cell Imbalance and IL-6 Profile in Patients With Unexplained Recurrent Spontaneous Abortion

Abstract

Regulatory T cells (Treg) and T helper 17 cells (Th17) are 2 distinct subsets of CD4⁺ T cells, which are mutually antagonistic in the immune response. Recently, dysregulation of these 2 cell subsets have been described in the pathogenesis of unexplained recurrent spontaneous abortion (URSA). The purpose of this study was to investigate whether the Treg/Th17 balance was perturbed in URSA patients and to explore contributing factors. We found that the proportion of Treg cells and expression of forkhead box P3 (Foxp3) messenger RNA (mRNA) were significantly lower in URSA patients than in healthy controls. However, the proportion of Th17 cells and expression of retinoid-related orphan nuclear receptor-γt (ROR-γt) mRNA were higher in URSA patients than in controls, revealing inverse correlation with Treg. The ratio of Treg/Th17 and Foxp3/ROR-γt decreased in patients with URSA compared to healthy controls. The serum levels of interleukin (IL)-6 and IL-17A were significantly higher, whereas IL-10 was lower in URSA patients compared with controls, and the level of IL-6 showed a positive correlation with Th17, ROR-γt and inverse correlation with Treg, Foxp3. The present study indicated that an imbalance between Treg and Th17 cells might be implicated in the pathogenesis of URSA and this seems to relate to elevation in serum IL-6 level.

Keywords: IL-6; T helper 17 cells; regulatory T cells; unexplained recurrent spontaneous abortion.