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口服表达螨和蟑螂主要变应原可减轻小鼠模型中特应性进程的进展。

Oral Administration of Expressing Mite and Cockroach Major Allergens Alleviates Progression of Atopic March in a Mouse Model.

作者信息

Lee Mey-Fann, Chen Yi-Hsing, Chiang Chu-Hui, Wu Chi-Sheng, Li Min-Hou, Wang Nancy M

机构信息

Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.

Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.

出版信息

Allergy Asthma Immunol Res. 2024 Sep;16(5):520-533. doi: 10.4168/aair.2024.16.5.520.

DOI:10.4168/aair.2024.16.5.520
PMID:39363770
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11450443/
Abstract

PURPOSE

Atopic march is defined as the development of atopic dermatitis in early childhood. We recently developed an atopic march mouse model through skin sensitization with aeroallergens from house dust mites and cockroaches. Using this model, this study aimed to evaluate the oral immunotherapy efficacy of harboring specific antigens on the progression of atopic march.

METHODS

Dust mite major allergen Der p 2 and cockroach Per a 2-372 were expressed in as a fusion recombinant clone (D2P2). -D2P2 was administered intragastrically to Aeroallergen patch-sensitized mice once a day for a total of 35 times. The immunological variables in sera, scratching behavior, airway hyperresponsiveness (AHR), and pathology of lungs and skin were evaluated.

RESULTS

Our data showed that s-D2P2 significantly lowered total immunoglobulin E levels, decreased scratch bouts, and relieved AHR compared with the control mice. Histological analysis of the skin and lung tissue demonstrated the therapeutic effects of -D2P2 to modulate immune responses via decreased eosinophil infiltration and reduced expression of key cytokines, interleukin (IL)-31 and IL-13, respectively.

CONCLUSIONS

The results imply that mucosal allergen-specific immunotherapy of -D2P2 is a more cost-effective alternative to conventional subcutaneous allergen-specific immunotherapy. This study provides a promising platform for the development of novel oral protein-based vaccines in the early prevention of allergies.

摘要

目的

特应性进程被定义为幼儿期特应性皮炎的发展。我们最近通过用屋尘螨和蟑螂的气传变应原进行皮肤致敏建立了一种特应性进程小鼠模型。利用该模型,本研究旨在评估携带特定抗原的口服免疫疗法对特应性进程进展的疗效。

方法

将尘螨主要变应原Der p 2和蟑螂Per a 2 - 372作为融合重组克隆(D2P2)进行表达。将s - D2P2每天一次经胃内给予气传变应原贴片致敏的小鼠,共给药35次。评估血清中的免疫变量、搔抓行为、气道高反应性(AHR)以及肺和皮肤的病理学变化。

结果

我们的数据表明,与对照小鼠相比,s - D2P2显著降低了总免疫球蛋白E水平,减少了搔抓发作次数,并缓解了AHR。皮肤和肺组织的组织学分析表明,s - D2P2通过分别减少嗜酸性粒细胞浸润和关键细胞因子白细胞介素(IL)- 31和IL - 13的表达来调节免疫反应,从而发挥治疗作用。

结论

结果表明,s - D2P2的黏膜变应原特异性免疫疗法是一种比传统皮下变应原特异性免疫疗法更具成本效益的替代方法。本研究为开发新型口服蛋白疫苗用于早期预防过敏提供了一个有前景的平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcd/11450443/35f21742f255/aair-16-520-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcd/11450443/0b10ab08e074/aair-16-520-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcd/11450443/6cde7b91d541/aair-16-520-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcd/11450443/0bbe531b4940/aair-16-520-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcd/11450443/62357229f933/aair-16-520-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcd/11450443/35f21742f255/aair-16-520-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcd/11450443/0b10ab08e074/aair-16-520-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcd/11450443/9f0a2de83bf2/aair-16-520-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcd/11450443/6cde7b91d541/aair-16-520-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcd/11450443/0fa507f5c97e/aair-16-520-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcd/11450443/62357229f933/aair-16-520-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcd/11450443/35f21742f255/aair-16-520-g007.jpg

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本文引用的文献

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An atopic dermatitis-like murine model by skin-brushed cockroach Per a 2 and oral tolerance induction by Lactococcus lactis-derived Per a 2.经皮刷蟑螂 Per a 2 诱导的特应性皮炎样小鼠模型和乳球菌衍生的 Per a 2 口服耐受诱导。
PLoS One. 2023 Sep 7;18(9):e0291162. doi: 10.1371/journal.pone.0291162. eCollection 2023.
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Indoor aeroallergens from American cockroaches and mites initiate atopic march via cutaneous contact in a murine model.室内过敏原,如美洲蟑螂和尘螨,可通过接触皮肤引发小鼠模型中的特应性进程。
PLoS One. 2023 Jul 27;18(7):e0289138. doi: 10.1371/journal.pone.0289138. eCollection 2023.
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特应性皮炎的非生物系统性治疗:现状与未来方向。
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Potential Anti-Allergy and Immunomodulatory Properties of LB 1022 Observed In Vitro and in an Atopic Dermatitis Mouse Model.LB 1022 在体外和特应性皮炎小鼠模型中表现出的潜在抗过敏和免疫调节特性。
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