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.