Reduced expression of indoleamine 2,3-dioxygenase participates in pathogenesis of preeclampsia via regulatory T cells

Abstract

Preeclampsia is a complex multi-organ disease and the leading cause of maternofetal morbidity and mortality. Low levels of indoleamine 2,3-dioxygenase (IDO) and diminished numbers of regulatory T cells (Tregs) have been separately reported to participate in the pathogenesis of preeclampsia. In the present study, we aimed to determine whether alterations in the expression of IDO, forkhead box P3 (Foxp3) and interleukin-18 (IL-18) contribute to the pathogenesis of preeclampsia, by measuring their levels in preeclamptic placentae and in placentae from healthy pregnant women as a control. IDO protein levels were determined by immunohistochemistry, while the mRNA levels of IDO, FoxP3 and IL-18 were measured by quantitative RT-PCR. The intensity of IDO immunostaining was lower in the preeclamptic placentae than in the normal controls, and was related to the clinical severity of the preeclampsia. Quantitative RT-PCR revealed that the IDO and IL-18 mRNA levels were reduced in a correlated manner the preeclamptic placentae compared to the controls, and that the levels of FoxP3 mRNA were consistently decreased in the preeclamptic group. A positive correlation betwen FoxP3 and IDO mRNA was found. The results of the study indicate that IL-18, IDO and FoxP3 mRNA levels were decreased in the preeclamptic placentae. Reduced IDO levels in preeclampsia may be partly influenced by IL-18, and result in the maladaptation of maternal tolerance and the pathogenesis of preeclampsia by directly reducing Tregs.