Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Iran J Allergy Asthma Immunol. 2023 Jun 16;22(3):233-244. doi: 10.18502/ijaai.v22i3.13051.
An imbalance between regulatory T (Treg) and T-helper (Th)-17 cells has been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19). Mesenchymal stem cells (MSCs) exert immunomodulatory properties through secreting exosomes. This study aimed to assess the effect of MSC-derived exosomes (MSC-Exo) on the differentiation of peripheral blood mononuclear cells (PBMCs) into Tregs from patients with COVID-19. Exosomes were isolated from adipose tissue-derived MSCs. PBMCs were separated from the whole blood of COVID-19 patients (n=20). Treg frequency was assessed before and 48 hours after treatment of PBMCs with MSC-Exo using flow cytometry. Expression of FOXP3 and cytokine genes, and the concentration of cytokines associated with Tregs, were assessed before and after treatment with MSC-Exo. The frequency of CD4+CD25+CD127- Tregs was significantly higher after treating PBMCs with MSC-Exo (6.695±2.528) compared to before treatment (4.981±2.068). The expressions of transforming growth factor (TGF)-β1, interleukin (IL)-10, and FOXP3 were significantly upregulated in MSC-Exo-treated PBMCs. The concentration of IL-10 increased significantly after treatment (994.7±543.9 pg/mL) of PBMCs with MSC-Exo compared with before treatment (563.5±408.6 pg/mL). The concentration of TGF-β was significantly higher in the supernatant of PBMCs after treatment with MSC-Exo (477.0±391.1 pg/mL) than PBMCs before treatment (257.7±226.3 pg/mL). MSC-Exo has the potential to raise anti-inflammatory responses by induction of Tregs, potentiating its therapeutic effects in COVID-19.
调节性 T（Treg）和辅助性 T 细胞 17（Th17）细胞之间的失衡与 2019 年冠状病毒病（COVID-19）的发病机制有关。间充质干细胞（MSCs）通过分泌外泌体发挥免疫调节作用。本研究旨在评估 MSC 衍生的外泌体（MSC-Exo）对 COVID-19 患者外周血单个核细胞（PBMC）向 Treg 分化的影响。外泌体从脂肪组织衍生的 MSC 中分离出来。从 COVID-19 患者的全血中分离 PBMC（n=20）。使用流式细胞术在 PBMC 用 MSC-Exo 处理前和 48 小时评估 Treg 频率。在用 MSC-Exo 处理前后评估 FOXP3 和细胞因子基因的表达以及与 Treg 相关的细胞因子的浓度。用 MSC-Exo 处理 PBMC 后 CD4+CD25+CD127- Treg 的频率明显高于处理前（6.695±2.528 对 4.981±2.068）。在 MSC-Exo 处理的 PBMC 中转化生长因子（TGF）-β1、白细胞介素（IL）-10 和 FOXP3 的表达明显上调。用 MSC-Exo 处理 PBMC 后 IL-10 的浓度明显升高（994.7±543.9 pg/mL 对 563.5±408.6 pg/mL）。用 MSC-Exo 处理 PBMC 后上清液中 TGF-β的浓度明显高于处理前（477.0±391.1 pg/mL 对 257.7±226.3 pg/mL）。MSC-Exo 通过诱导 Treg 产生具有升高抗炎反应的潜力，从而增强其在 COVID-19 中的治疗作用。
