Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 3 2023 06 16 233 244 Morteza Motallebnezhad Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Ali Hazrati Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Hadi Esmaeili Gouvarchin Ghaleh Applied Virology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran Nematollah Jonaidi-Jafari Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Sanaz Abbaspour-Aghdam Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Kosar Malekpour Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Mehdi Yousefi Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Hossein Samadi Kafil Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Farhad Jadidi-Niaragh Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Leila Roshangar Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Hamed Valizadeh Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran Morteza Izadi Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Majid Ahmadi Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 2022 09 29 2023 01 03 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. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3666 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3666/1945