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The imbalance of Th17/Treg axis involved in the pathogenesis of preeclampsia

免疫系统 RAR相关孤儿受体γ 发病机制 外周血单个核细胞 免疫学 流式细胞术 维甲酸 子痫前期 白细胞介素17 逆转录聚合酶链式反应 白细胞介素 受体 小RNA 病理生理学 孤儿受体 内分泌学 生物 转录因子 内科学 医学 信使核糖核酸 细胞因子 基因 FOXP3型 怀孕 体外 遗传学
作者
Shadi Eghbal‐Fard,Mehdi Yousefi,Hanieh Heydarlou,Majid Ahmadi,Simin Taghavi,Aliakbar Movasaghpour,Farhad Jadidi‐Niaragh,Bahman Yousefi,Sanam Dolati,Mohammad Hojjat‐Farsangi,Reza Rikhtegar,Mohammad Nouri,Leili Aghebati‐Maleki
出处
期刊:Journal of Cellular Physiology [Wiley]
卷期号:234 (4): 5106-5116 被引量:108
标识
DOI:10.1002/jcp.27315
摘要

Abstract Problem Inappropriate activation of the immune system, particularly the imbalance of T‐helper type 17 (Th17)/regulatory T (Treg) cells is thought to play considerable roles in preeclampsia (PE). To investigate the probable effects of the adaptive immune system in the pathophysiology of PE, we analyzed the dynamic changes of Th17/Treg cells, cytokines profile, and transcription pattern of Th17/Treg‐related genes and microRNAs (miRNAs) in 50 women suffering from PE in comparison with 50 healthy pregnant women. Methods Expressions of cytokines, specific transcription factors, and related miRNAs were measured by real‐time polymerase chain reaction (PCR). Enzyme‐linked immunosorbent assay (ELISA) was used to test the interleukin (IL)‐17, IL‐23, IL‐6, and IL‐10 and transforming growth factor β in serum and supernatant of peripheral blood mononuclear cells (PBMCs). The frequency of Th17 and Treg cells were determined by flow cytometry. Results PE patients exhibited a decreased number of Treg cells ( p = 0.006), while Th17 cells were increased ( p = 0.004). Forkhead box P3 and IL‐10 mRNA expressions were reduced ( p = 0.0001 and 0.0028, respectively), while expressions of retinoic acid receptor‐related orphan nuclear receptor γt, IL‐17, IL‐23, and IL‐6 were enhanced ( p < 0.0001, 0.0018, 0.0014, and 0.027, respectively). ELISA results also showed increased levels of IL‐6, IL‐17, and IL‐23 ( p = 0.022, 0.0005, 0.0081, respectively), and decreased levels of IL‐10 in the supernatant of PBMCs of PE patients compared with control group ( p = 0.0011). There was significant upregulation of miR‐106b and miR‐326 ( p = 0.0048 and 0.028, respectively) in PE patients in comparison with the control group. Conclusions These findings suggest that imbalance of Th17/Treg cells, regulated possibly via microRNAs, may be involved in the pathogenesis of PE, emphasizing on the importance of these cells in feto‐maternal immune cross‐talk.

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