Department of ORL-HNS, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Plasma Medicine and Surgical Implants Center, School of Medicine, Tongji University, Shanghai, China.
Scand J Immunol. 2024 Dec;100(6):e13416. doi: 10.1111/sji.13416. Epub 2024 Oct 29.
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 CD4Foxp3IL-17, CD4Foxp3IL-17 and CD4Foxp3IL-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. CD4Foxp3IL-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(CD4IFN-γcells)/Th2(CD4IL-4cells) balance, reduced CD4IL-17 and increased CD4IL-10 and CD4TGF-β cells. The MFI of IL-10 and TGF-β in CD4CD25CD127 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.
间充质干细胞衍生的细胞外囊泡 (MSC-EVs) 在多种临床情况下显示出有希望的免疫调节能力。然而,MSC-EVs 在变应性鼻炎 (AR) 中的潜在调节机制仍未得到探索。本研究旨在探讨 MSC-EVs 在 AR 患者中的免疫调节作用。从 AR 患者中分离外周血单个核细胞 (PBMC)。使用流式细胞术评估健康对照组和 AR 患者外周血 CD4Foxp3IL-17、CD4Foxp3IL-17 和 CD4Foxp3IL-17 T 细胞的数量。通过 ELISA 和流式细胞术检测上清液中 IFN-γ、IL-4、IL-17 和 IL-10 细胞因子来确定 MSC-EVs 的治疗效果。在 MSC-EVs 处理后,计算 PBMC 中 T 细胞上 IL-10、IL-17 和 TGF-β 的平均荧光强度 (MFI)。通过基因本体论 (GO) 和京都基因与基因组百科全书 (KEGG) 分析进行 microRNA 的生物信息学分析。AR 组 PBMC 中 CD4Foxp3IL-17 T 细胞的表达更高,Treg/Th17 的平衡向 Th17 细胞倾斜。来自 AR 患者的上清液显示,MSC-EVs 治疗可上调 IL-10 和 IFN-γ,并下调 IL-4 和 IL-17。EVs 治疗有效地重建了 Th1(CD4IFN-γ 细胞)/Th2(CD4IL-4 细胞)平衡,减少了 CD4IL-17,增加了 CD4IL-10 和 CD4TGF-β 细胞。CD4CD25CD127 T 细胞中 IL-10 和 TGF-β 的 MFI 更高,而 IL-17 的水平较低。生物信息学分析表明,TGF-β、Wnt 信号通路和 STAT5 转录因子可能从机制上支持 MSC-EVs 的免疫调节作用。本研究介绍了 MSC-EVs 在 AR 患者 PBMC 中的免疫调节作用。研究结果为 AR 提供了一种新的治疗策略。
Expert Rev Mol Med. 2025-6-30