Development of allergic rhinitis immunotherapy using antigen-loaded small extracellular vesicles
Development of allergic rhinitis immunotherapy using antigen-loaded small extracellular vesicles
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利用抗原负载的细胞外小泡免疫治疗变应性鼻炎的进展
DOI：
10.1016/j.jconrel.2022.03.016
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发表时间：
2022-03-24
影响因子：
10.8
通讯作者：
Takakura, Yoshinobu
中科院分区：
文献类型：
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作者：
Liu, Wen;Ota, Maki;Takakura, Yoshinobu
变应性鼻炎是由Th1/Th2平衡的破坏引起的，其中由变应原诱导的Th2免疫反应超过Th1免疫反应，最终导致IgE介导的过敏反应。在这项研究中，我们使用小细胞外小泡(SEV)，即颗粒为100 nm的细胞膜小泡，作为过敏原(卵蛋白，OVA)和CpG DNA(一种可以诱导Th1免疫反应的佐剂)的同时递送载体，用于治疗变应性鼻炎。成功制备了携带CpG DNA和OVA的SEV(CpG-OVA-SEV)。CpG-OVA-SEV的平均粒径为90 nm，平均Zeta电位为-30 mV。CpG DNA修饰不影响树突状细胞对SEV的摄取，CpG-OVAsEV可激活树突状细胞。将CpG-OVA-SEV接种于小鼠鼻咽相关淋巴组织(NALT)，经鼻腔给药后主要被CD11c阳性细胞摄取。在变应性鼻炎小鼠模型中，鼻腔注射CpG-OVA-SEV可显著提高OVA特异性抗体效价，提示Th1/2平衡发生了改变。此外，与对照组相比，CpG-OVA-SEV组的过敏症状有所减轻。此外，小鼠血清中的IgE分泌量减少。因此，CpG-OVA-SEVS有可能成为治疗变应性鼻炎的有效方法。
Allergic rhinitis is caused by a breakdown of the Th1/Th2 balance, in which the allergen-induced Th2 immune response predominates over the Th1 immune response, culminating in IgE-mediated anaphylaxis. In this study, we used small extracellular vesicles (sEVs), cell-derived membrane vesicles with a particle size of 100 nm, as simultaneous delivery carriers for allergens (ovalbumin, OVA) and CpG DNA, an adjuvant that can induce a Th1 immune response, for the treatment of allergic rhinitis. sEVs loaded with CpG DNA and OVA(CpG-OVA-sEVs) were successfully prepared. CpG-OVA-sEVs possessed an average particle size of 90 nm and average zeta potential of-30 mV. CpG DNA modification did not influence the uptake of sEVs by dendritic cells and CpG-OVAsEV can activate dendritic cells. The CpG-OVA-sEVs were delivered to the nasopharynx-associated lymphoid tissue (NALT) of mice and were primarily taken up by the CD11c positive cells after intranasal administration. Intranasally administering CpG-OVA-sEVs significantly enhanced OVA-specific IgG antibody titers in mice models of allergic rhinitis, suggesting a transformed Th1/2 balance. Moreover, The CpG-OVA-sEV administration alleviated allergic symptoms compared to the control group. Further, the amount of IgE secreted in mouse serum decreased. Thus, CpG-OVA-sEVs could be a useful therapeutic method for treating allergic rhinitis.