Ribeiro Vanessa R, Romao-Veiga Mariana, Romagnoli Graziela G, Matias Mariana L, Nunes Priscila R, Borges Vera Therezinha M, Peracoli Jose C, Peracoli Maria Terezinha S
Department of Gynaecology and Obstetrics, Medical School, Botucatu Sao Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil.
Department of Microbiology and Immunology, Institute of Biosciences, Botucatu Sao Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil.
Immunology. 2017 Sep;152(1):163-173. doi: 10.1111/imm.12757. Epub 2017 Jun 19.
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.
子痫前期(PE)是一种产科病理状态,其特征是先天性和适应性免疫系统异常激活,这依赖于辅助性T细胞亚群的失衡。本研究旨在采用定量逆转录聚合酶链反应(RT-PCR)和流式细胞术技术,评估PE孕妇外周血淋巴细胞中辅助性T细胞1型(Th1)/辅助性T细胞2型(Th2)/辅助性T细胞17型(Th17)/调节性T细胞(Treg)转录因子的基因和蛋白表达,以及这些CD4 T细胞亚群在PE孕妇血浆中产生的细胞因子谱,这些孕妇被分为早发型PE(n = 20)、晚发型PE(n = 20)和血压正常的孕妇(n = 20)。结果显示,与晚发型PE组和血压正常组相比,早发型PE女性中表达RORc转录因子(Th17)的CD4 T细胞百分比更高,而表达FoxP3(Treg)的细胞百分比更低。与晚发型PE组相比,早发型PE女性细胞中GATA-3转录因子的基因表达更低。早发型PE组内源性血浆白细胞介素-6(IL-6)、IL-17和肿瘤坏死因子-α水平显著高于晚发型PE组和血压正常组,而IL-4(Th2谱)和IL-22(Th17谱)在研究组之间无显著差异。子痫前期孕妇内源性转化生长因子-β和IL-10水平显著低于相同孕周的血压正常组,早发型和晚发型PE之间存在显著差异。结果表明,PE女性CD4 T细胞亚群中炎症和抗炎谱之间存在失衡,早发型PE(被认为是PE的严重形式)中向Th17谱极化。