Department of Otorhinolaryngology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.
Department of Environmental Medical Biology, Catholic Kwandong University College of Medicine, Gangneung 25601, Republic of Korea.
Int J Mol Sci. 2024 Sep 30;25(19):10524. doi: 10.3390/ijms251910524.
Although mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are as effective as MSCs in the suppression of allergic airway inflammation, few studies have evaluated the immunomodulatory capacity of MSC-derived EVs in patients with asthma. Thus, we assessed the effects of adipose stem cell (ASC)-derived EVs on cytokine expression and regulatory T cells (Tregs) in peripheral blood mononuclear cells (PBMCs) of asthmatic patients. PBMCs (1 × 10 cells/mL) were isolated from asthmatic patient and healthy controls and co-cultured with 1 μg/mL of ASC-derived EVs. Th (T helper) 1-, Th2-, and Treg-related cytokine expression, fluorescence-activated cell sorting analysis of CD4CD25FOXP3 T cells, and co-stimulatory molecules were analyzed before and after ASC-derived EV treatment. The expression levels of IL-4 and costimulatory molecules such as CD83 and CD86 were significantly higher in PBMCs of asthmatic patients than in control PBMCs. However, ASC-derived EV treatment significantly decreased the levels of interleukin (IL)-4 and co-stimulatory molecules such as CD83 and CD86 in the phytohemagglutinin (PHA)-stimulated PBMC of asthmatic patients. Furthermore, ASC-derived EVs remarkably increased the transforming growth factor-β (TGF-β) levels and expression of Tregs in the PBMC of asthmatic patients. ASC-derived EVs induce Treg expansion and have immunomodulatory effects by downregulating IL-4 and upregulating TGF-β in PBMCs of asthmatic patients.
虽然间充质干细胞（MSC）衍生的细胞外囊泡（EVs）在抑制过敏性气道炎症方面与 MSC 一样有效，但很少有研究评估 MSC 衍生 EVs 在哮喘患者中的免疫调节能力。因此，我们评估了脂肪干细胞（ASC）衍生的 EVs 对哮喘患者外周血单个核细胞（PBMC）中细胞因子表达和调节性 T 细胞（Tregs）的影响。从哮喘患者和健康对照者中分离 PBMC（1×10 个细胞/mL），并与 1μg/mL 的 ASC 衍生 EV 共培养。在 ASC 衍生 EV 处理前后分析 Th（辅助性 T 细胞）1、Th2 和 Treg 相关细胞因子表达、CD4CD25FOXP3 T 细胞荧光激活细胞分选分析以及共刺激分子。与健康对照者的 PBMC 相比，哮喘患者的 PBMC 中 IL-4 和共刺激分子（如 CD83 和 CD86）的表达水平明显更高。然而，ASC 衍生的 EV 处理可显著降低 PHA 刺激的哮喘患者 PBMC 中白细胞介素（IL）-4 和共刺激分子（如 CD83 和 CD86）的水平。此外，ASC 衍生的 EVs 可显著增加哮喘患者 PBMC 中转化生长因子-β（TGF-β）水平和 Tregs 的表达。ASC 衍生的 EVs 通过下调 IL-4 并上调 TGF-β 来诱导 Treg 扩增，并在哮喘患者的 PBMC 中发挥免疫调节作用。
