经皮递送耐受性纳米颗粒诱导哮喘治疗的有效免疫耐受
2024/01/26
摘要
引起特异性抗原免疫耐受，用于过敏性或自身免疫性疾病的治疗，是一种具有吸引力的策略。在这里，我们通过激发抗原特异性免疫耐受性，研究了经皮微针贴片对过敏性哮喘的保护效应。我们制造了可生物降解的耐受性纳米颗粒（tNPs），其中装载有一个模型抗原卵清蛋白（OVA）和一种免疫调节剂雷帕霉素，然后通过离心将tNPs填充到微针尖中，形成持续释放的微针。经皮免疫后，微针成功将载体输送到皮肤中，并持续释放超过96小时。重要的是，这些微针诱导了特异性抗原的调节性T细胞（Treg），降低了促炎细胞因子和抗体的水平，同时增加了抗炎细胞因子，最终导致免疫稳态的恢复。肺组织分析表明，持续释放的微针显著减少了嗜酸性粒细胞的浸润，减少了粘液和胶原蛋白的积聚，并显著缓解了哮喘症状。我们的结果表明，基于持续释放的微针的经皮传递系统可以诱导抗原特异性的免疫耐受，具有改善依从性和疗效的特点，为过敏性和自身免疫性疾病的治疗提供了一种新的治疗策略。
Transdermally delivered tolerogenic nanoparticles induced effective immune tolerance for asthma treatment
Jiaxuan Zhao, Penghui He, Min Jiang, Chunting He, Yuanhao Zhao, Zhihua Zhang, Zhibing Zhang, Guangsheng Du, Xun Sun
Abstract
Induction of antigen-specific immune tolerance for the treatment of allergic or autoimmune diseases is an attractive strategy. Herein, we investigated the protective effect of a transdermal microneedle patch against allergic asthma by stimulating allergen-specific immune tolerance. We fabricated biodegradable tolerogenic nanoparticles (tNPs) that are loaded with a model allergen ovalbumin (OVA) and an immunomodulator rapamycin, and filled the tNPs into microneedle tips by centrifugation to form sustained-release microneedles. After intradermal immunization, the microneedles successfully delivered the cargos into the skin and sustainedly released them for over 96 h. Importantly, the microneedles induced allergen-specific regulatory T cells (Treg), decreased the levels of pro-inflammatory cytokines and antibodies while increased anti-inflammation cytokines, finally leading to restored immune homeostasis. The lung tissue analysis illustrated that the sustained-release microneedles significantly reduced the infiltration of eosinophils, decreased the accumulation of mucus and collagen, and significantly relived asthma symptoms. Our results suggested that the sustained-release microneedle-based transdermal delivery system can induce antigen-specific immune tolerance with improved compliance and efficacy, providing a new therapeutic strategy for the treatment of allergic and autoimmune diseases.
引起特异性抗原免疫耐受，用于过敏性或自身免疫性疾病的治疗，是一种具有吸引力的策略。在这里，我们通过激发抗原特异性免疫耐受性，研究了经皮微针贴片对过敏性哮喘的保护效应。我们制造了可生物降解的耐受性纳米颗粒（tNPs），其中装载有一个模型抗原卵清蛋白（OVA）和一种免疫调节剂雷帕霉素，然后通过离心将tNPs填充到微针尖中，形成持续释放的微针。经皮免疫后，微针成功将载体输送到皮肤中，并持续释放超过96小时。重要的是，这些微针诱导了特异性抗原的调节性T细胞（Treg），降低了促炎细胞因子和抗体的水平，同时增加了抗炎细胞因子，最终导致免疫稳态的恢复。肺组织分析表明，持续释放的微针显著减少了嗜酸性粒细胞的浸润，减少了粘液和胶原蛋白的积聚，并显著缓解了哮喘症状。我们的结果表明，基于持续释放的微针的经皮传递系统可以诱导抗原特异性的免疫耐受，具有改善依从性和疗效的特点，为过敏性和自身免疫性疾病的治疗提供了一种新的治疗策略。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(J Control Release. 2024 Jan 10:S0168-3659(24)00022-1. doi: 10.1016/j.jconrel.2024.01.018.)
(J Control Release. 2024 Jan 10:S0168-3659(24)00022-1. doi: 10.1016/j.jconrel.2024.01.018.)
Transdermally delivered tolerogenic nanoparticles induced effective immune tolerance for asthma treatment
Jiaxuan Zhao, Penghui He, Min Jiang, Chunting He, Yuanhao Zhao, Zhihua Zhang, Zhibing Zhang, Guangsheng Du, Xun Sun
Abstract
Induction of antigen-specific immune tolerance for the treatment of allergic or autoimmune diseases is an attractive strategy. Herein, we investigated the protective effect of a transdermal microneedle patch against allergic asthma by stimulating allergen-specific immune tolerance. We fabricated biodegradable tolerogenic nanoparticles (tNPs) that are loaded with a model allergen ovalbumin (OVA) and an immunomodulator rapamycin, and filled the tNPs into microneedle tips by centrifugation to form sustained-release microneedles. After intradermal immunization, the microneedles successfully delivered the cargos into the skin and sustainedly released them for over 96 h. Importantly, the microneedles induced allergen-specific regulatory T cells (Treg), decreased the levels of pro-inflammatory cytokines and antibodies while increased anti-inflammation cytokines, finally leading to restored immune homeostasis. The lung tissue analysis illustrated that the sustained-release microneedles significantly reduced the infiltration of eosinophils, decreased the accumulation of mucus and collagen, and significantly relived asthma symptoms. Our results suggested that the sustained-release microneedle-based transdermal delivery system can induce antigen-specific immune tolerance with improved compliance and efficacy, providing a new therapeutic strategy for the treatment of allergic and autoimmune diseases.
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度普利尤单抗治疗哮喘儿童的长期安全性及有效性评估（自由哮喘研究）：一项开放标签扩展研究
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儿童和青少年哮喘的心理干预
