Association between cytokine profile and transcription factors produced by T‐cell subsets in early‐ and late‐onset pre‐eclampsia

Abstract

Pre-eclampsia (PE) is an obstetric pathology characterized by abnormal activation of the innate and adaptive immune systems dependent on the imbalance of T helper subsets. The present study aimed to evaluate the gene and protein expression of T helper type 1 (Th1)/Th2/Th17/regulatory T (Treg) cell transcription factors in peripheral blood lymphocytes from pregnant women with PE employing quantitative RT-PCR and flow cytometry techniques, as well as the cytokine profile produced by these CD4 T-cell subsets in the plasma of pregnant women with PE, classified as early-onset PE (n = 20), late-onset PE (n = 20) and normotensive pregnant women (n = 20). Results showed a higher percentage of CD4 T cells expressing the RORc transcription factor (Th17) and a lower percentage of cells expressing FoxP3 (Treg) in women with early-onset PE compared with late-onset PE and normotensive groups. A lower gene expression of GATA-3 transcription factor was detected in cells of women with early-onset PE compared with the late-onset PE group. Endogenous plasma levels of interleukin-6 (IL-6), IL-17 and tumour necrosis factor-α were significantly higher in the early-onset PE group than in the late-onset PE and normotensive groups, whereas IL-4 (Th2 profile) and IL-22 (Th17 profile), were not significantly different between the studied groups. The endogenous levels of transforming growth factor-β and IL-10 were significantly lower in the pre-eclamptic than in the normotensive groups of the same gestational age, with a significant difference between early- and late-onset PE. The results show that in women with PE there is an imbalance between inflammatory and anti-inflammatory profiles in CD4 T-cell subsets, with polarization to Th17 profiles in the early-onset PE, considered as the severe form of PE.

Regulatory T and T helper 17 cells: Their roles in preeclampsia

“…Ribeiro et al () in 2017 exhibited that pregnant women with early‐onset PE presented higher percentage of CD4+ T cells expressing the RORc transcription factor and a remarkable reduction in the percentage of Treg cells expressing FoxP3 in relation to the late‐onset PE group, therefore approving the severity of the disease before the 34th week of gestation. This Treg/Th17 imbalance can be accountable for the activation of the inflammatory responses that is more noticeable in early‐onset than in late‐onset PE.…”

Prenatal inflammation exposure-programmed cardiovascular diseases and potential prevention

“…Early onset of maternal higher blood pressure or preeclampsia during pregnancy can lead to an imbalance between inflammatory and anti-inflammatory profiles in CD4 + T cell subsets, accompanied by higher plasma levels of interleukin-6 (IL-6), IL-17 and tumor necrosis factor (TNF)-α in mothers (Ribeiro, et al, 2017). This imbalance can affect early childhood blood pressures and cardiovascular health in the offspring.…”

Disturbed Maternal Immune Milieu Early in Pregnancy Could Predict Later Development of Pre-Eclampsia and Differentiate Its Severity Grades.

“…Similarly, Ribeiro et al (25) found elevated plasma levels of IL-6, IL-17 and TNF-α with decreased plasma levels of IL-10 can differentiate between early-onset and late-onset PE, while Daneva et al (29) reported that in pregnancies complicated by PE there are increased levels of proinflammatory cytokines and changes are most pronounced in mild PE, while changes in anti-inflammatory cytokines are more pronounced in severe PE.…”

“…Also, Cornelius et al (23) experimentally found on transfer of Th17 cells resulting from reduced uterine perfusion in induced tissue oxidative stress, increased serum IL-6 and causes increased blood pressure and intrauterine growth restriction and concluded that autoimmune status associated with Th17 cells may have a role in pathogenesis of PE. Thereafter, Zhang et al (24) found plasma concentrations of IL-17 and IL-22 were significantly increased along with a decreased plasma IL-10 concentration in severe PE patients and Ribeiro et al (25) found plasma levels of IL-6, IL-17 and TNF-α were significantly higher whereas IL-10 levels were significantly lower in PE than in normotensive women. Also, Poordast et al…”