In the course of the coronavirus disease 2019 (COVID‐19), raising and reducing the function of Th17 and Treg cells, respectively, elicit hyperinflammation and disease progression. The current study aimed to evaluate the responses of Th17 and Treg cells in COVID‐19 patients compared with the control group. Forty COVID‐19 intensive care unit (ICU) patients were compared with 40 healthy controls. The frequency of cells, gene expression of related factors, as well as the secretion levels of cytokines, were measured by flow cytometry, real‐time polymerase chain reaction, and enzyme‐linked immunosorbent assay techniques, respectively. The findings revealed a significant increase in the number of Th17 cells, the expression levels of related factors (RAR‐related orphan receptor gamma [RORγt], IL‐17, and IL‐23), and the secretion levels of IL‐17 and IL‐23 cytokines in COVID‐19 patients compared with controls. In contrast, patients had a remarkable reduction in the frequency of Treg cells, the expression levels of correlated factors (Forkhead box protein P3 [FoxP3], transforming growth factor‐β [TGF‐β], and IL‐10), and cytokine secretion levels (TGF‐β and IL‐10). The ratio of Th17/Treg cells, RORγt/FoxP3, and IL‐17/IL‐10 had a considerable enhancement in patients compared with the controls and also in dead patients compared with the improved cases. The findings showed that enhanced responses of Th17 cells and decreased responses of Treg cells in 2019‐n‐CoV patients compared with controls had a strong relationship with hyperinflammation, lung damage, and disease pathogenesis. Also, the high ratio of Th17/Treg cells and their associated factors in COVID‐19‐dead patients compared with improved cases indicates the critical role of inflammation in the mortality of patients.
Bacteriophages are specific antagonists to bacterial hosts. These viral entities have attracted growing interest as optimal vaccine delivery vehicles. Phages are well-matched for vaccine design due to being highly stable under harsh environmental conditions, simple and inexpensive large scale production, and potent adjuvant capacities. Phage vaccines have efficient immunostimulatory effects and present a high safety profile because these viruses have made a constant relationship with the mammalian body during a long-standing evolutionary period. The birth of phage display technology has been a turning point in the development of phage-based vaccines. Phage display vaccines are made by expressing multiple copies of an antigen on the surface of immunogenic phage particles, thereby eliciting a powerful and effective immune response. Also, the ability to produce combinatorial peptide libraries with a highly diverse pool of randomized ligands has transformed phage display into a straightforward, versatile and high throughput screening methodology for the identification of potential vaccine candidates against different diseases in particular microbial infections. These libraries can be conveniently screened through an affinity selection-based strategy called biopanning against a wide variety of targets for the selection of mimotopes with high antigenicity and immunogenicity. Also, they can be panned against the antiserum of convalescent individuals to recognize novel peptidomimetics of pathogen-related epitopes. Phage display has represented enormous promise for finding new strategies of vaccine discovery and production and current breakthroughs promise a brilliant future for the development of different phage-based vaccine platforms.
In novel coronavirus disease 2019 (COVID‐19), the increased frequency and overactivation of T helper (Th) 17 cells and subsequent production of large amounts of proinflammatory cytokines result in hyperinflammation and disease progression. The current study aimed to investigate the therapeutic effects of nanocurcumin on the frequency and responses of Th17 cells in mild and severe COVID‐19 patients. In this study, 40 severe COVID‐19 intensive care unit‐admitted patients and 40 patients in mild condition were included. The frequency of Th17 cells, the messenger RNA expression of Th17 cell‐related factors (RAR‐related orphan receptor γt, interleukin [IL]‐17, IL‐21, IL‐23, and granulocyte‐macrophage colony‐stimulating factor), and the serum levels of cytokines were measured in both nanocurcumin and placebo‐treated groups before and after treatment. A significant decrease in the number of Th17 cells, downregulation of Th17 cell‐related factors, and decreased levels of Th17 cell‐related cytokines were found in mild and severe COVID‐19 patients treated by nanocurcumin compared to the placebo group. Moreover, the abovementioned parameters were significantly decreased in the nanocurcumin‐treated group after treatment versus before treatment. Curcumin could reduce the frequency of Th17 cells and their related inflammatory factors in both mild and severe COVID‐19 patients. Hence, it could be considered as a potential modulatory compound in improving the patient's inflammatory condition.
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 |
CD4CD25 regulatory T (Treg) cells and Th17 cells play important roles in peripheral immunity. Immune responses are main elements in the pathogenesis of ischemic stroke (IS). The contribution of Th17 cells in IS patients has not been proved, and whether the balance of Treg/Th17 cells is changed in IS patients remains unidentified. In the present study, we studied Th17 and Treg cell frequency, cytokine secretion, expression of transcription factors, and microRNAs related to Th17 and Treg cells differentiation, which is compared between IS patients and control group. Thirty patients with IS and 30 individuals as control group were enrolled in this study. The frequency of Th17 and Treg lymphocytes, the expression of transcription factors and microRNAs related to these cells, and the serum levels of associated cytokines were assessed by flow cytometry, real-time PCR, and ELISA, respectively. A significant reduction in proportion of peripheral Treg cell frequency and the levels of TGF-β and FOXP3 expression were observed in patients with IS compared with controls, while the proportions of Th17 were increased dramatically, and these effects were along with increases in the levels of IL-17A and RORγt expression in IS patients. The levels of mir-326 and mir-106b-25 expression were increased in patients with IS. These studies suggest that the increase in proportion of Th17 cells and decrease in Treg cells might contribute to the pathogenesis of IS. Manipulating the balance between Tregs and Th17 cells might be helpful for the treatment of IS.
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