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建立和鉴定哮喘小鼠模型及葎草花粉变应性的皮下免疫治疗。

Establishment and characterization of murine models of asthma and subcutaneous immunotherapy for Humulus pollen allergy.

机构信息

Department of Allergy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment on Allergic Diseases, Beijing, China.

出版信息

Immun Inflamm Dis. 2021 Jun;9(2):443-455. doi: 10.1002/iid3.405. Epub 2021 Jan 12.

DOI:10.1002/iid3.405
PMID:33434413
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8127558/
Abstract

INTRODUCTION

Humulus pollen is an important cause of allergic asthma in East Asia. There have been some murine models for Humulus pollen allergy established by intraperitoneal (IP) sensitization and nasal drip stimulation, but they were not comprehensive enough. Here, we used atomized inhalation for challenge and compared the subcutaneous (SC) and IP sensitization routes to determine the optimal method to establish a model of asthma induced by Humulus pollen. Subsequently, we tried to develop a rapid subcutaneous immunotherapy (SCIT) model for Humulus allergy.

METHODS

BALB/c Mice were sensitized through the SC or IP route, with respective reference to previously established sensitization methods and allergen dosing, and challenged with nebulized Humulus pollen extract to induce asthma. To compare the two sensitization methods, airway hyperresponsiveness (AHR), inflammatory cell infiltration, allergen-specific serum immunoglobulin (Ig)E (sIgE) levels, cytokine levels, and lung histopathology were assessed. The effects of SCIT (once every other day for 16 days) on airway inflammation, AHR, sIgE, and allergen-specific serum IgG2a (sIgG2a) levels were evaluated by using the model established in this study.

RESULTS

Although mice sensitized by the SC or IP routes both showed AHR and airway inflammation, the SC route elicited significantly higher levels of sIgE, eosinophil inflammation, and T helper type 2 cytokines, compared with the IP route. SCIT in the treatment group significantly reduced the titers of sIgE, enhanced the titers of sIgG2a, and effectively alleviated pulmonary inflammation and AHR, compared with the vehicle group.

CONCLUSIONS

The SC route can be used to establish a murine model of Humulus pollen allergy that recapitulates the characteristics of clinical allergic asthma. Short-term SCIT can significantly improve symptoms and pathophysiology in asthmatic mice.

摘要

简介

葎草花粉是东亚地区过敏性哮喘的一个重要病因。已经有一些通过腹腔(IP)致敏和鼻滴刺激建立的葎草花粉过敏的小鼠模型,但它们不够全面。在这里,我们使用雾化吸入进行挑战,并比较了皮下(SC)和 IP 致敏途径,以确定建立葎草花粉诱导哮喘模型的最佳方法。随后,我们试图开发一种快速皮下免疫治疗(SCIT)模型来治疗葎草过敏。

方法

BALB/c 小鼠通过 SC 或 IP 途径致敏,分别参照先前建立的致敏方法和过敏原剂量,并通过雾化葎草花粉提取物进行激发,以诱导哮喘。为了比较两种致敏方法,评估气道高反应性(AHR)、炎症细胞浸润、过敏原特异性血清免疫球蛋白(Ig)E(sIgE)水平、细胞因子水平和肺组织病理学。通过使用本研究建立的模型,评估 SCIT(每隔一天皮下注射 16 天)对气道炎症、AHR、sIgE 和过敏原特异性血清 IgG2a(sIgG2a)水平的影响。

结果

尽管通过 SC 或 IP 途径致敏的小鼠均表现出 AHR 和气道炎症,但与 IP 途径相比,SC 途径诱导的 sIgE、嗜酸性粒细胞炎症和辅助性 T 细胞 2 型细胞因子水平显著升高。与对照组相比,治疗组的 SCIT 显著降低了 sIgE 的滴度,提高了 sIgG2a 的滴度,有效缓解了肺部炎症和 AHR。

结论

SC 途径可用于建立一种能够重现临床变应性哮喘特征的葎草花粉过敏小鼠模型。短期 SCIT 可显著改善哮喘小鼠的症状和病理生理学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a1/8127558/32ce671e2fd6/IID3-9-443-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a1/8127558/19dfcb6a0cb3/IID3-9-443-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a1/8127558/32ce671e2fd6/IID3-9-443-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a1/8127558/009069a55b3a/IID3-9-443-g003.jpg
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