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模拟抗原驱动的哮喘在啮齿动物模型中-我们能有多接近?

Mimicking Antigen-Driven Asthma in Rodent Models-How Close Can We Get?

机构信息

Center of Allergy & Environment (ZAUM), Technical University of Munich (TUM) and Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.

Molecular Allergology/Vice President's Research Group, Paul-Ehrlich-Institut, Langen, Germany.

出版信息

Front Immunol. 2020 Sep 30;11:575936. doi: 10.3389/fimmu.2020.575936. eCollection 2020.

Abstract

Asthma is a heterogeneous disease with increasing prevalence worldwide characterized by chronic airway inflammation, increased mucus secretion and bronchial hyperresponsiveness. The phenotypic heterogeneity among asthmatic patients is accompanied by different endotypes, mainly Type 2 or non-Type 2. To investigate the pathomechanism of this complex disease many animal models have been developed, each trying to mimic specific aspects of the human disease. Rodents have classically been employed in animal models of asthma. The present review provides an overview of currently used Type 2 vs. non-Type 2 rodent asthma models, both acute and chronic. It further assesses the methods used to simulate disease development and exacerbations as well as to quantify allergic airway inflammation, including lung physiologic, cellular and molecular immunologic responses. Furthermore, the employment of genetically modified animals, which provide an in-depth understanding of the role of a variety of molecules, signaling pathways and receptors implicated in the development of this disease as well as humanized models of allergic inflammation, which have been recently developed to overcome differences between the rodent and human immune systems, are discussed. Nevertheless, differences between mice and humans should be carefully considered and limits of extrapolation should be wisely taken into account when translating experimental results into clinical use.

摘要

哮喘是一种异质性疾病,在全球范围内患病率不断增加,其特征为慢性气道炎症、黏液分泌增加和支气管高反应性。哮喘患者的表型异质性伴随着不同的内型,主要是 2 型或非 2 型。为了研究这种复杂疾病的发病机制,已经开发了许多动物模型,每个模型都试图模拟人类疾病的特定方面。啮齿动物经典地被用于哮喘的动物模型中。本综述概述了目前使用的 2 型与非 2 型的啮齿动物哮喘模型,包括急性和慢性模型。它进一步评估了用于模拟疾病发展和加重以及量化变应性气道炎症的方法,包括肺生理学、细胞和分子免疫反应。此外,还讨论了遗传修饰动物的应用,这些动物提供了对多种分子、信号通路和受体在疾病发展中的作用的深入了解,以及最近开发的变应性炎症的人源化模型,这些模型旨在克服啮齿动物和人类免疫系统之间的差异。然而,应该仔细考虑老鼠和人类之间的差异,并在将实验结果转化为临床应用时明智地考虑外推的局限性。

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Metabolic Dysfunction and Asthma: Current Perspectives.代谢功能障碍与哮喘:当前观点
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The Global Initiative for Asthma (GINA): 25 years later.全球哮喘倡议(GINA):25 年后。
Eur Respir J. 2019 Aug 29;54(2). doi: 10.1183/13993003.00598-2019. Print 2019 Aug.

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