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An imbalance between regulatory T (Treg) and T-helper (Th)-17 cells has been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19). Mesenchymal stem cells (MSCs) exert immunomodulatory properties through secreting exosomes. This study aimed to assess the effect of MSC-derived exosomes (MSC-Exo) on the differentiation of peripheral blood mononuclear cells (PBMCs) into Tregs from patients with COVID-19. Exosomes were isolated from adipose derived -- tissue MSCs. PBMCs were separated from the whole blood of COVID-19 patients (n=20). Treg frequency was assessed before and 48 hours after treatment of PBMCs with MSC-Exo using flow cytometry. Expression of FOXP3 and cytokine genes, and the concentration of cytokines associated with Tregs, were assessed before and after treatment with MSC-Exo. The frequency of CD4+CD25+CD127- Tregs was significantly higher after treating PBMCs with MSC-Exo (6.695±2.528) compared to before treatment (4.981±2.068). The expressions of transforming growth factor (TGF)-β1, interleukin (IL)-10, and FOXP3 were significantly upregulated in MSC-Exo--treated PBMCs. The concentration of IL-10 increased significantly after treatment (994.7±543.9 pg/mL) of PBMCs with MSC-Exo compared with before treatment (563.5±408.6 pg/mL). The concentration of TGF-β was significantly higher in the supernatant of PBMCs after treatment with MSC-Exo (477.0±391.1 pg/mL) than PBMCs before treatment (257.7±226.3 pg/mL). MSC-Exo has the potential to raise anti-inflammatory responses by induction of Tregs, potentiating its therapeutic effects in COVID-19. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Recurrent miscarriage (RM) has a multifactorial etiology mainly due to chromosomal abnormalities and immunological factors. Treating RM has remained to be a challenging issue and the role of intravenous immunoglobulin (IVIG) in treating RM is still controversial. Materials and Methods: This study aimed to evaluate the changes in natural killer (NK) cells' frequency and cytotoxicity in patients with RM who received the IVIG therapy. A total of 78 women with a history of three or more recurrent miscarriages were included and their peripheral blood was drawn in case of positive pregnancy test. On the same date, 400 mg/kg of IVIG was administrated intravenously in 38 women and it continued every four weeks through weeks 30–32 of gestation. The remaining 40 patients with RM were included to be the untreated control group. Then, the effects of IVIG on NK cell frequency, cytotoxic activity, and the expression of inhibitory and activating receptors in the patients with RM, pre and posttreatment were assessed. Results: NK cells percentage and cytotoxicity were significantly reduced in the IVIG‐treated patients after 32 weeks of gestation (p < 0.0001). Expression levels of inhibitory receptors was increased, however, the expression levels of activating receptors were significantly decreased after the IVIG therapy. Pregnancy outcome after the treatment was significantly higher (86.8%) in the IVIG‐treated patients than controls (45%; p = 0.0006). Conclusion: Our results suggested that women with RM may benefit from IVIG as a therapeutic approach and the frequency and functional status of peripheral NK cells may serve as a valuable predictive factor of therapy response. [ABSTRACT FROM AUTHOR]

Impaired inflammatory immune cells have been implicated in the pathogenesis of Behcet'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. [ABSTRACT FROM AUTHOR]