Altered Expression of STAT3, RORγt, and IL-17A Proteins and Th17 Cell in Intrahepatic Cholestasis of Pregnancy

Abstract

Background: Intrahepatic cholestasis of pregnancy (ICP) is a disorder specifically associated with pregnancy. Recent evidence suggests that the T helper 17 (Th17) cell population is related to a maternal and foetal immune imbalance associated with ICP. However, there has been insufficient attention paid to the potential roles of signal transducer and activator of transcription 3 (STAT3) and RAR-related orphan receptor gamma (RORγt) in modulations of Th17 cell in ICP. Accordingly, the purpose of our study was to investigate the alterations of Th17 cell in placenta and peripheral blood of patients with ICP and correlations between Th17 cell and STAT3, RORγt, interleukin (IL)-17A in ICP. Methods: Nine pregnant women with ICP and nine women with normal pregnancy served as the ICP and control groups, respectively. STAT3, RORγt, and IL-17A expression were examined by immunohistochemistry and western blotting in placental tissue. Flow cytometry was used to quantify Th17 cell in blood of peripheral circulation. We compared data between groups using Chi-square tests or paired t tests. Pearson or Spearman coefficients were used to measure correlations. Results: STAT3, RORγt, and IL-17A were mainly expressed in the trophoblasts of the two groups of patients. Comparatively to the control group, placental levels of STAT3, RORγt, and IL-17A proteins were significantly elevated in ICP group, as was maternal levels of Th17 cell in peripheral blood. Moreover, placental IL-17A protein level showed significantly positive relationships with placental STAT3 (r = 0.97, p = 2e-05) and RORγt (r = 0.91, p = 0.01) protein in control group, however, not in ICP group (STAT3, r = 0.5, p = 0.17; RORγt, r = 0.62, p = 0.07). Conclusions: Women with ICP showed an increase in Th17 cells in comparison to women with normal pregnancies. STAT3 and RORγt may increase Th17 cell proliferation and differentiation, appears to be altered in ICP. ICP may be adversely affected by excessive accumulation of Th17 cell.