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间充质干细胞来源的细胞外囊泡对调节过敏性鼻炎患者外周血单个核细胞中调节性 T 细胞和 Th1/Th2 失衡的免疫调节作用。

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.

机构信息

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.

出版信息

Scand J Immunol. 2024 Dec;100(6):e13416. doi: 10.1111/sji.13416. Epub 2024 Oct 29.


DOI:10.1111/sji.13416
PMID:39473031
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 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.

摘要

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。

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