Disturbed Th17/Treg balance, cytokines, and miRNAs in peripheral blood of patients with Behcet’s disease

Abstract

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.

Inhibition of CD83 Alleviates Systemic Inflammation in Herpes Simplex Virus Type 1-Induced Behçet’s Disease Model Mouse

“…Several studies of BD have demonstrated that a significant increase of serum IL-17 is an indicator of reactive or recurrence of infection [25, 26]. To determine whether CD83 siRNA could improve the symptoms of BD by downregulating IL-17, plasma IL-17 levels were measured in CD83 siRNA-treated BD mice by ELISA.…”

The emerging role of microRNA in regulating the mTOR signaling pathway in immune and inflammatory responses

“…Thus, disclosing the mechanisms that control the balance between Treg/Th17 cells is a critical factor in pathogenesis, prognosis and therapy of several immune-related disorders. [110][111][112] Likewise, a large number of studies have reported that miRNAs play a pivotal role in regulating the mTOR signaling pathway and fine-tuning the development of both Tregs and Th17 cells. A forward genetic screen for identifying miRNAs involved in the regulation of Treg cell differentiation revealed that out of 130 candidates, 29 miRNAs had a negative effect and 10 had a positive effect.…”

Promoter methylation of Bax and Bcl2 genes and their expression in patients with Behcet’s disease

“…Th‐17 cells are a relatively new subset of T helper cells mainly producing IL‐17A, IL‐17F, IL‐22 and TNF‐α (Annunziato, Cosmi, Liotta, Maggi, & Romagnani, ). Recent data have proven the involvement of IL‐17 and Th17 cell responses in the pathogenesis of Behcet's disease and shown the Behcet activated by high serum levels of interleukins 6, 10 17, 23, as well as Th17 cells (Abolhasani, Gholizadeh Ghaleh Aziz, Khabbazi, & Alipour, ; Ahmadi et al, ; Alipour, Nouri, et al, ; Alipour, Sakhinia, et al, ; Chi et al, ). Therapeutic methods such as interferon alfa and anti‐TNF‐α (Tumour necrosis Factor alpha) agents that are effective in Behcet's disease with eye contamination have revealed that they inhibit responses of Th17 cell (Liu, Yang, Wang, Li, & Kijlstra, ; Sugita et al, ).…”