Exosomes from bronchoalveolar fluid of tolerized mice prevent allergic reaction
Exosomes from bronchoalveolar fluid of tolerized mice prevent allergic reaction
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DOI：
10.4049/jimmunol.181.2.1519
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发表时间：
2008-07-15
影响因子：
4.4
通讯作者：
Batanero, Eva
中科院分区：
文献类型：
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作者：
Prado, Noela;Marazuela, Eva G.;Batanero, Eva
外来体是源自由多种细胞类型分泌的多泡体的纳米囊泡。外泌体促进免疫或诱导耐受的双重能力促使其在临床上用作针对不同人类疾病的疫苗接种载体。在本研究中，使用小鼠模型确定来自耐受小鼠的变应原特异性外泌体对变应原诱导的过敏反应的发展的影响。小鼠通过呼吸道暴露于橄榄花粉过敏原Ole e 1而耐受。通过完善的过滤和超离心程序从动物的支气管肺泡灌洗液中分离外泌体样囊泡，通过电子显微镜、蛋白质印迹和FACS分析进行表征，并在预防方案中进行评估。为此，在致敏/攻击Ole e 1前1周，用致耐受性外泌体或未处理外泌体鼻内处理BALB/c小鼠作为对照。收集血液、肺和脾并分析免疫应答。鼻内给药致耐受性外泌体可抑制IgE反应、Th 2细胞因子产生和气道炎症（过敏的主要特征）的发展，并在体内维持特异性长期保护作用。这种保护作用与调节细胞因子TGF-β表达的伴随增加有关。这些观察结果表明，外来体可以诱导耐受性和保护小鼠免受过敏性致敏。因此，基于外泌体的疫苗可以代表人类过敏性疾病常规疗法的替代方案。
Exosomes are nanovesicles originating from multivesicular bodies that are secreted by a variety of cell types. The dual capability of exosomes to promote immunity or to induce tolerance has prompted their clinical use as vehicles for vaccination against different human diseases. In the present study, the effect of allergen-specific exosomes from tolerized mice on the development of allergen-induced allergic response was determined using a mouse model. Mice were tolerized by respiratory exposure to the olive pollen allergen Ole e 1. Exosome-like vesicles were isolated from bronchoalveolar lavage fluid of the animals by the well-established filtration and ultracentrifugation procedure, characterized by electron microscopy, Western blot, and FACS analyses, and assessed in a prophylactic protocol. To this end, BALB/c mice were intranasally treated with tolerogenic exosomes or naive exosomes as control, 1 wk before sensitization/challenge to Ole e 1. Blood, lungs, and spleen were collected and analyzed for immune responses. Intranasal administration of tolerogenic exosomes inhibited the development of IgE response, Th2 cytokine production, and airway inflammation-cardinal features of allergy- and maintained specific long-term protection in vivo. This protective effect was associated with a concomitant increase in the expression of the regulatory cytokine TGF-beta. These observations demonstrate that exosomes can induce tolerance and protection against allergic sensitization in mice. Thus, exosome-based vaccines could represent an alternative to conventional therapy for allergic diseases in humans.