Decrease in Regulatory T-cells and Increase in T Helper 17 Cells in Women With Recurrent Spontaneous Abortion

Abstract BackgroundAppearance of improper immune responses against the fetus and/or inadequate immunoregulatory mechanisms during pregnancy may lead to recurrent spontaneous abortion (RSA). TH17 cells play a significant role in inducing inflammation, autoimmune disease, and acute transplant rejection, while regulatory T (Treg) cells moderate the function of immune system in order to retain homeostasis.MethodsThis case-control study was designed to evaluate TH17 as well as Treg cells in 25 women with RSA and 25 age-matched healthy non-pregnant women. Flow cytometric assay was performed using monoclonal antibodies to detect CD4+CD25+ Treg cells (CD25dim and CD25bright). FoxP3 and RORγt expressions were compared using real-time PCR, and pro-inflammatory and anti-inflammatory cytokines were measured by ELISA kits. Independent-samples T test was employed for statistical analysis. ResultsThe ratio of CD4+CD25bright T cells was remarkably lower in women with RSA (P<0.05), and CD4+CD25dim T cells did not show any significant difference among the groups (P>0.05). RORγt was up-regulated, and FoxP3 was down-regulated significantly in case group (P<0.05). The significant increase of IL-6 and IL-17 as well as the decrease of TGF-β was indicated in RSA group (P<0.05). Also, IL-10 did not vary among the groups (P>0.05). ConclusionThese remarks prove that the decrease in regulatory factors such as CD4+CD25bright T-cells, TGF-β and FoxP3 expression may disrupt immune tolerance and homeostasis during pregnancy. Also, the environment rich in RORγt, IL-6, and IL-17 suggests the detrimental role of TH17 cells, which may lead to fetal rejection.