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. K E Y W O R D S interleukin, microRNA, preeclampsia, regulatory T-cell, T-helper 17 cell J Cell Physiol. 2019;234:5106-5116. wileyonlinelibrary.com/journal/jcp 5106 |

Impaired inflammatory immune cells have been implicated in the pathogenesis ofBehcet's disease (BD). In the current study, we aimed to evaluate the frequency of T helper (Th) 17 and regulatory T (Treg) cells, cytokine secretion, the expression of transcription factors related to Th17 and Treg cells, and microRNAs (miRNAs) targeting these transcription factors in BD patients. Blood samples from 47 BD patients and 58 healthy subjects were drawn, and the peripheral blood mononuclear cells (PBMCs) were separated and isolated. The frequency of Th17 and Treg cells was assessed using flow cytometry. Transcription factors related to these cells and miRNAs targeting these transcription factors were quantified using real-time polymerase chain reaction. Finally, the levels of associated cytokines were measured using enzyme-linked immunosorbent assay. A significant reduction in the percentage of Treg cell frequency and the levels of interleukin (IL)-10 and forkhead box P3 messenger RNA (mRNA) expressions were observed. The proportion of Th17 cells was notably increased, which was accompanied by a increased levels of IL-17, IL-23, and retinoic acid-related orphan receptor ɣ (RORɣt) mRNA expressions in BD patients. The level of Th17-associated cytokines in the supernatant was found to be elevated in BD patients. T-cell-associated miRNA expression levels, miR-25, miR-106b, miR-326, and miR-93 were significantly upregulated, while miR-146a and miR-155 levels were lower in PBMCs of patients with BD when compared with the controls. The increase in the proportion of Th17 cells alongside the decrease in Treg cells are possibly the involving factors in the pathogenesis of BD.Therefore, the evaluation of immune cells and related miRNA profile may serve as both prognostic biomarker and therapeutic approach in treating patients with BD.

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Recurrent pregnancy loss (RPL) is a one of the most common obstetrical complications. Since, the successful pregnancy occurs in T helper 2 (Th2)‐dominant situation and since, Th1 type immunity is related to pregnancy failure, we investigated the effects of cyclosporine on Th1 and Th2 cells in RPL women. Totally, 76 RPL patients (38 women as treated group and 38 as control group) were included in this study. Flow cytometry was utilized to analyze the frequency of Th1 and Th2 in blood samples. Also, real‐time polymerase chain reaction was carried out to assess the messenger RNA (mRNA) expression of transcription factors and enzyme‐linked immunosorbent assay was used to evaluate Th1 and Th2 related cytokines. Significant decrease in Th1 frequency (p = 0.0004), Th1/Th2 ratio (p < 0.0001), T‐bet mRNA expression (p < 0.0001), interferon‐γ (p = 0.0007), and tumor necrosis factor α (p = 0.0002) secretion level were observed in cyclosporine group. Moreover, significant increase in Th2 frequency (p < 0.0001), mRNA expression of GATA binding protein 3 (p = 0.0001), and interleukin 10 secretion level (p = 0.0027) was also evident in treated group. At the end of the investigation, 31 (81.5%) patients in cyclosporine‐treated group had successful childbirth when compared with 16 (42.1%) women in control group (p = 0.0001). Given this, cyclosporine treatment for RPL patients with elevated Th1/Th2 ratio can result in improved pregnancy outcome.

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ProblemTo investigate whether metabolic syndrome (MetS) is associated with exacerbation of inflammatory responses in preeclamptic (PE) patients, the dynamic changes of Th17 and Treg cells, monocytes, cytokines, and transcription pattern of inflammasome‐related genes were analyzed in 35 women with PE suffering from MetS in comparison to 38 PE women without MetS and healthy pregnant women.Method of studyExpression of inflammasome‐related genes, cytokines, and also TLR4 was measured using real‐time PCR. Serum and medium supernatant cytokines levels of PBMCs and serum levels of HMGB1 and Caspase‐1 were also evaluated by ELISA. Monocytes, Th17, and Treg cells frequency were also determined by flow cytometry.ResultPE women with MetS exhibited increased percentage of non‐classical and intermediate monocytes and Th17 cells (P = 0.025). Furthermore, decreased Treg cells frequency was also observed in PE women with MetS compared to PE women (P = 0.019). The mRNA expression of inflammasome‐related genes (Caspase‐1, NLRP3, HMGB1), TLR4, IL‐1β, IL‐6, IL‐17, IL‐18, and TNF‐α was significantly higher in PE patients with MetS than that of the healthy pregnant individuals (P < 0.0001) and PE patients (P < 0.0001). Serum levels of TGF‐β and TNF‐α in PE patients with MetS were increased compared to other two groups, while IL‐10 levels were significantly reduced. A significant sFlt (P = 0.016), Caspase‐1 (P = 0.012), HMGB1 (P = 0.016) upregulation, and VEGF (P = 0.023) downregulation were also observed in the serum of PE women having MetS compared to PE women.ConclusionMetS is closely related to the exacerbation of inflammatory reactions in PE. This study indicates that, in order to diminish the systemic features of PE, prior to conceive and start a pregnancy, MetS should be severely considered and managed.

Epithelial-mesenchymal transition (EMT) is a phenomenon in which epithelial cells lose their cell-to-cell connection and are detached from the base membrane. EMT is fundamental for many biological processes such as embryonic development and neurogenesis. It also plays a significant role in cancer progression and metastasis. EMT regulation occurs through a sophisticated network of transcription regulations that include many signaling pathways. The exact mechanism of cancer gene regulation has not been understood yet. However, it is interesting to study the role of microRNAs and epigenetics mechanism in the cancer development. In this review, the transcription regulation of EMT and the analysis of possible overlap between microRNAs and their targets which are involved in the cancer development are scrutinized.