通过舌下免疫疗法，将过敏原负载到间充质干细胞衍生的外泌体中作为有效载体来调节免疫应答。
Immune response modulation by allergen loaded into mesenchymal stem cell-derived exosomes as an effective carrier through sublingual immunotherapy.
机构信息
Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Air Pollution and Respiratory Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
出版信息
Immunobiology. 2023 May;228(3):152361. doi: 10.1016/j.imbio.2023.152361. Epub 2023 Feb 27.
BACKGROUND
Allergen-specific sublingual immunotherapy (SLIT) was considered an interesting needle-free alternative for subcutaneous immunotherapy (SCIT). Mesenchymal stem cell (MSC)-derived exosomes were introduced as potent nanoscale delivery systems with immunomodulatory potentials. The current study investigated the therapeutic efficacy of SLIT using ovalbumin (OVA)-enriched MSC-derived exosomes formulation in a murine model of allergic asthma.
MATERIAL AND METHODS
MSCs were harvested from mice adipose tissues. Then, exosomes were isolated, and OVA-loaded exosomes were prepared. Following sensitization, Balb/c mice received therapeutic formulation (10 μg/dose OVA-containing MSC-derived exosomes) twice a week for two months. Serum OVA-specific IgE levels as well as IFN-γ, IL-4, and TGF-β secretions by cultured splenocytes were measured by ELISA. Also, lung tissue underwent histopathologic analysis, and the numbers of inflammatory cells and eosinophils in nasopharyngeal lavage fluid (NALF) were examined.
RESULTS
SLIT using OVA-enriched exosomes significantly reduced IgE levels and IL-4 production, while the secretion of IFN-γ and TGF-β were significantly elevated. Also, a decrease was observed in the numbers of total cells and eosinophils in the NALF, and lower levels of perivascular and peribronchiolar inflammation and cellular infiltrations were observed in the lung tissue.
CONCLUSION
SLIT using OVA-loaded exosomes improved immunomodulatory responses and efficiently alleviated allergic inflammation.
背景
变应原特异性舌下免疫疗法（SLIT）被认为是一种替代皮下免疫疗法（SCIT）的无针疗法。间充质干细胞（MSC）衍生的外泌体作为具有免疫调节潜力的有效纳米级递药系统被引入。本研究通过卵清蛋白（OVA）富集 MSC 衍生外泌体配方在变应性哮喘小鼠模型中研究了 SLIT 的治疗效果。
材料和方法
从小鼠脂肪组织中收获 MSC。然后，分离出外泌体，并制备负载 OVA 的外泌体。致敏后，Balb/c 小鼠每周接受两次治疗制剂（10μg/dose 含 OVA 的 MSC 衍生外泌体），共两个月。通过 ELISA 测量血清 OVA 特异性 IgE 水平以及培养的脾细胞分泌的 IFN-γ、IL-4 和 TGF-β。还对肺组织进行了组织病理学分析，并检查了鼻咽灌洗液（NALF）中炎症细胞和嗜酸性粒细胞的数量。
结果
使用 OVA 富集外泌体的 SLIT 显著降低了 IgE 水平和 IL-4 的产生，而 IFN-γ 和 TGF-β 的分泌显著增加。此外，NALF 中的总细胞和嗜酸性粒细胞数量减少，肺组织中的血管周围和细支气管周围炎症和细胞浸润水平降低。
结论
使用负载 OVA 的外泌体的 SLIT 改善了免疫调节反应，并有效地缓解了过敏炎症。
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