Asthma is a chronic eosinophilic airway disease characterized by type 2 helper T cell-driven inflammation. Adipose stem cells (ASCs) and the ASC culture supernatant are known to improve allergic airway inflammation; however, the immunomodulatory effects of ASC-derived extracellular vesicles (EVs) on allergic airway diseases remain unclear. Thus, we assessed the effects of ASC-derived EVs on allergic airway inflammation in a mouse model of asthma. EVs were isolated from the culture supernatant of murine ASCs and characterized. Six-week-old female C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection and challenged intranasally with OVA. Before the OVA challenge, 10 μg/50 μl of ASC-derived EVs was administered intranasally to the experimental group. ASC-derived EVs significantly attenuated airway hyperresponsiveness (AHR) in asthmatic mice (). ASC-derived EVs resulted in a remarkable reduction of the total number of inflammatory cells () and eosinophils () in the bronchoalveolar lavage fluid (BALF), the degree of eosinophilic lung inflammation (), and the serum total and OVA-specific immunoglobulin (Ig)E ( and ) and total IgG1 (). Interleukin- (IL-) 4 was significantly inhibited with ASC-derived EV pretreatment in the BALF and lung draining lymph nodes (LLNs) ( and ). Furthermore, ASC-derived EV administration resulted in a significant increase of the regulatory T cell (Treg) populations in LLNs. ASC-derived EVs alleviated AHR and allergic airway inflammation caused by the induction of Treg expansion in a mouse model of asthma. There seems to be a role for ASC-derived EVs as a modifier in allergic airway disease.

中文翻译：

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来自脂肪干细胞的鼻内给药的细胞外囊泡在哮喘小鼠模型中具有免疫调节作用

哮喘是一种慢性嗜酸性粒细胞气道疾病，其特征是 2 型辅助性 T 细胞驱动的炎症。已知脂肪干细胞 (ASC) 和 ASC 培养上清液可改善过敏性气道炎症；然而，ASC 衍生的细胞外囊泡 (EV) 对过敏性气道疾病的免疫调节作用仍不清楚。因此，我们评估了 ASC 衍生的 EV 对哮喘小鼠模型中过敏性气道炎症的影响。从小鼠 ASC 的培养上清液中分离出 EV，并对其进行表征。六周大的雌性 C57BL/6 小鼠通过腹腔注射对卵清蛋白 (OVA) 敏感，并用 OVA 进行鼻内攻击。在 OVA 挑战之前，10  μ g/50  μ1 升 ASC 衍生的 EV 被鼻内施用于实验组。ASC 衍生的 EV 显着减弱了哮喘小鼠的气道高反应性 (AHR)。）。ASC 衍生的 EV 导致炎症细胞总数显着减少（)和嗜酸性粒细胞 ()在支气管肺泡灌洗液 (BALF) 中，嗜酸性肺部炎症的程度 ()，以及血清总和 OVA 特异性免疫球蛋白 (Ig)E ( 和 )和总 IgG1 (）。白细胞介素- (IL-) 4 在 BALF 和肺引流淋巴结 (LLN) 中被 ASC 衍生的 EV 预处理显着抑制。 和 ）。此外，ASC 衍生的 EV 给药导致 LLN 中调节性 T 细胞（Treg）群体的显着增加。ASC 衍生的 EV 减轻了哮喘小鼠模型中由诱导 Treg 扩增引起的 AHR 和过敏性气道炎症。ASC 衍生的 EV 似乎可以作为过敏性气道疾病的调节剂。