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 |

Toll-like receptors (TLRs) are innate immune cells receptors. They are expressed on leukocytes, epithelial cells, and more particularly on placental immune cells and chorion trophoblast. Upregulation of innate immune response occurs during normal pregnancy, but its excessive activity is involved in the pathology of pregnancy complications including pregnancy-induced hypertension and pre-eclampsia (PE). The recent studies about the overmuch inflammatory responses and aberrant placentation are associated with increased expression of TLRs in PE patients. This review has tried to focus on the relationship between some activities of TLRs and the risk of preeclampsia development.

Aim Ankylosing spondylitis (AS) is an inflammatory rheumatic disease with increased bone mass in the main sites of inflammation. Regulatory T (Treg) cells have been reported to involve in pathology of AS. This study designed at investigating the effects of nanocurcumin on Treg cell responses in peripheral blood (PB) of AS patients. Methods Test group including 12 AS patients received nanocurcumin daily for 4 months and control group including 12 patients received placebo. The frequency of Treg was measured by flow cytometry. The expression levels of FoxP3 and several associated microRNAs (miRNAs; miR‐27, miR‐17, and miR‐146a) and cytokines including Interleukin‐10 (IL‐10), TGF‐β, and IL‐6 were assessed by real‐time polymerase chain reaction. Furthermore, enzyme‐linked immunosorbent assay was done to determine the secretion levels of cytokines. Results After treatment with nanocurcumin the frequency of Treg cells in AS patients increased significantly. The RT‐PCR data indicated that the expression of miR‐17 and miR‐27 were significantly decreased following nanocurcumin treatment while miR‐146a and FoxP3 were significantly increased. Moreover, nanocurcumin‐treated group had high levels of IL‐10 and TGF‐β and low levels of IL‐6 production than control group. Conclusion The findings suggested that dysregulation of Treg cells in PB influences the AS development and nanocurcumin therapy could regulate the Treg cells, and so could be useful in the treatment of AS and may be other autoimmune diseases. This study is registered with IRCT.ir, number IRCT2017052927520N7.

Preeclampsia (PE) is characterized by hypertension and proteinuria. It occurs in an around 3% to 5% of all pregnancies worldwide. The fetus is kind of semiallograft to the maternal host; immune system components encounter fetal antigens and develop adverse immune responses. Recently, it has been observed that the immune system plays an important role in PE. In the current study, we have tried to investigate the role of follicular helper T (Tfh) cells in the pathogenesis of PE. Blood samples of 49 PE women and 50 healthy controls were collected. Peripheral blood mononuclear cells were isolated, cells were cultured, and then RNA was extracted. Autoantibody and secretory cytokine levels were analyzed by ELISA. Tfh frequency and transcription levels of the related molecules and cytokine were assessed by flow cytometry and real-time PCR, respectively. The frequency of circulating Tfh cell in PE women was significantly higher compared with the healthy pregnant woman (Tfh cells with CD4 + ICOS + , P = 0.0064 and Tfh cells with CD4 + CXCR5 + , P = 0.029). Moreover, mRNA expression levels of CXCR5, BCL6, IL-21, and IL-6 (P = 0.0006, P = 0.008, P = 0.0063, and P = 0.027, respectively) were upregulated in PE patients. Furthermore, IL-6 (P = 0.0014) and IL-21 (P = 0.0059) levels in both group were assayed and the results showed increased in patient group. We also measured autoantibody levels including antiphospholipid antibodies (P = 0.0001), anticardiolipin antibodies (P = 0.0004), anti-TPO (P = 0.0008), anti-TG (P = 0.001) in circulation of PE group, which were higher than the control group. This study provided insights into the involvement of Tfh cells in etiology and pathogenesis of PE, probably by developing autoantibodies. K E Y W O R D S autoantibody, cytokine, follicular helper T cell, preeclampsia J Cell Biochem. 2019;120:3845-3852.wileyonlinelibrary.com/journal/jcb

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