Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 6 2023 12 28 561 574 Sajad Dehnavi Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran AND Department of Immunology, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran AND Infectious Diseases Research Center, Aja University of Medical Sciences, Tehran, Iran Maryam Dadmanesh Infectious Diseases Research Center, Aja University of Medical Sciences, Tehran, Iran AND Department of Infectious Diseases, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran Negin Hosseini Rouzbahani Department of Immunology, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran AND Infectious Diseases Research Center, Aja University of Medical Sciences, Tehran, Iran Mahmood Karimi Department of Pulmonology, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran Ali Asadirad Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran AND Cancer Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Mohammad Gholami Infectious Diseases Research Center, Aja University of Medical Sciences, Tehran, Iran AND Department of Medical Microbiology, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran Khodayar Ghorban Department of Immunology, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran 2023 02 07 2023 11 05 Increasing the efficacy of allergen-specific intranasal immunotherapy (INIT) has recently been the main goal of several studies to establish this route as a safe delivery method through mucosal pathways. In this case, the present study evaluated the potential of INIT using ovalbumin (OVA)-loaded mesenchymal stromal/stem cell (MSC)-derived exosomes (Exo-OVA) in an allergic asthma mouse model. Together with control groups, sensitized Balb/c mice underwent intranasal immunotherapy with Exo-OVA (10 μg OVA per dose) for three consecutive weeks. Serum-specific immunoglobulin E (IgE) levels, transforming growth factor-beta (TGF-β), interleukin (IL)-4, and interferon-gamma (IFN-γ) production by cultured spleen cells, lung histopathologic analysis, and nasopharyngeal lavage fluid cellular examinations were then conducted. The results showed that INIT using Exo-OVA significantly increased IFN-γ and TGF-β secretion, while allergen-specific IgE and IL-4 production were dramatically decreased compared to the control group receiving phosphate-buffered saline. In addition, the eosinophil and total cell counts in the nasopharyngeal lavage fluid were reduced, and inflammatory conditions and cell accumulation in lung tissue were ameliorated. In conclusion, the Exo-OVA improved the INIT efficacy compared to free OVA. Therefore, this formulation could be introduced as an effective approach for immunomodulatory purposes with a shorter treatment duration and reduced side effects. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3767 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3767/2001