Immunomodulatory effect of mesenchymal stem cells‐derived extracellular vesicles to modulate the regulatory T cells and Th1/Th2 imbalance in peripheral blood mononuclear cells of patients with allergic rhinitis

Abstract Mesenchymal stem cell‐derived extracellular vesicles (MSC‐EVs) have shown promising immunomodulatory capabilities for a variety of clinical conditions. However, the potential regulatory mechanisms of MSC‐EVs in allergic rhinitis (AR) remain unexplored. The present study was designed to investigate the immunomodulatory effect of MSC‐EVs in patients with AR. Peripheral blood mononuclear cells (PBMCs) were isolated from AR patients. The number of peripheral CD4 + Foxp3 + IL‐17 + , CD4 + Foxp3 + IL‐17 − and CD4 + Foxp3 − IL‐17 + T cells in healthy controls and AR patients were evaluated using flow cytometry. Therapeutic effect of MSC‐EVs was determined by detecting IFN‐γ, IL‐4, IL‐17 and IL‐10 cytokines in supernatant by ELISA and flow cytometry. The mean fluorescence intensity (MFI) was calculated in PBMCs for IL‐10, IL‐17 and TGF‐β on T cells after MSC‐EVs treatment. Bioinformatic analysis of microRNA was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. CD4 + Foxp3 + IL‐17 + T cells expression in PBMCs was higher in the AR group and the balance of Treg/Th17 was tilted towards Th17 cells. Supernatant from AR patients revealed that MSC‐EVs treatment upregulated IL‐10 and IFN‐γ, and downregulated IL‐4 and IL‐17. EVs treatment effectively re‐established Th1(CD4 + IFN‐γ + cells)/Th2(CD4 + IL‐4 + cells) balance, reduced CD4 + IL‐17 + and increased CD4 + IL‐10 + and CD4 + TGF‐β + cells. The MFI of IL‐10 and TGF‐β in CD4 + CD25 + CD127 − T cells were higher, whereas lower levels of IL‐17 were observed. Bioinformatic analysis revealed that the TGF‐β, Wnt signalling pathways and STAT5 transcription factor might mechanistically support the immunomodulatory effect of MSC‐EVs. This study presents the immunomodulatory effect of MSC‐EVs in PBMCs from AR patients. The results provide a new therapeutic strategy for AR.