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严重哮喘的新兴治疗靶点和临床前模型。

Emerging therapeutic targets and preclinical models for severe asthma.

机构信息

Centre for Inflammation, Centenary Institute and University of Technology Sydney , Sydney, Australia.

Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and the University of Newcastle , Newcastle, Australia.

出版信息

Expert Opin Ther Targets. 2020 Sep;24(9):845-857. doi: 10.1080/14728222.2020.1786535. Epub 2020 Jul 7.

DOI:10.1080/14728222.2020.1786535
PMID:32569487
Abstract

INTRODUCTION

Asthma is a heterogeneous disease with complex multifactorial causes. It is possible to subclassify asthma into different phenotypes that have distinct immunological features. Eosinophilic asthma is a well-known phenotype of severe asthma; however, a large body of clinical and experimental evidence strongly associates persistent airway inflammation, including the accumulation of neutrophils in the bronchial mucosa, and resistance to corticosteroid therapy and non-Type-2 immune responses with severe asthma. Importantly, mainstay therapies are often ineffective in severe asthma and effective alternatives are urgently needed.

AREAS COVERED

Here, we discussed recently developed mouse models of severe asthma that recapitulates key features of the disease in humans. We also provide findings from clinically relevant experimental models that have identified potential therapeutic targets for severe asthma. The most relevant publications on the topic of interest were selected from PubMed.

EXPERT COMMENTARY

Increasing the understanding of disease-causing mechanisms in severe asthma may lead to the identification of novel therapeutic targets and the development of more effective therapies. Intense research interest into investigating the pathophysiological mechanisms of severe asthma has driven the development and interrogation of a myriad of mouse models that aim to replicate hallmark features of severe asthma in humans.

摘要

简介

哮喘是一种具有复杂多因素病因的异质性疾病。可以将哮喘分为具有不同免疫学特征的不同表型。嗜酸性粒细胞性哮喘是一种众所周知的严重哮喘表型;然而,大量的临床和实验证据强烈表明持续性气道炎症与严重哮喘相关,包括中性粒细胞在支气管黏膜中的积聚,以及对皮质类固醇治疗和非 2 型免疫反应的抵抗。重要的是,严重哮喘的主要治疗方法往往无效,迫切需要有效的替代方法。

涵盖领域

在这里,我们讨论了最近开发的模拟人类严重哮喘关键特征的小鼠模型。我们还提供了来自临床相关实验模型的发现,这些模型确定了严重哮喘的潜在治疗靶点。从 PubMed 中选择了与感兴趣主题最相关的出版物。

专家评论

深入了解严重哮喘的致病机制可能会导致发现新的治疗靶点和开发更有效的治疗方法。对严重哮喘病理生理机制的研究兴趣日益浓厚,推动了众多旨在模拟人类严重哮喘标志性特征的小鼠模型的开发和研究。

相似文献

1
Emerging therapeutic targets and preclinical models for severe asthma.严重哮喘的新兴治疗靶点和临床前模型。
Expert Opin Ther Targets. 2020 Sep;24(9):845-857. doi: 10.1080/14728222.2020.1786535. Epub 2020 Jul 7.
2
Mouse models of severe asthma: Understanding the mechanisms of steroid resistance, tissue remodelling and disease exacerbation.重度哮喘的小鼠模型:了解类固醇抵抗、组织重塑和疾病加重的机制。
Respirology. 2017 Jul;22(5):874-885. doi: 10.1111/resp.13052. Epub 2017 Apr 11.
3
Mechanisms and treatments for severe, steroid-resistant allergic airway disease and asthma.重度、类固醇抵抗性过敏性气道疾病和哮喘的机制与治疗方法。
Immunol Rev. 2017 Jul;278(1):41-62. doi: 10.1111/imr.12543.
4
Investigating MIF in Mouse Models of Severe Corticosteroid-Resistant Neutrophilic Asthma.在严重皮质类固醇抵抗性嗜中性粒细胞性哮喘小鼠模型中研究巨噬细胞迁移抑制因子
Methods Mol Biol. 2020;2080:203-212. doi: 10.1007/978-1-4939-9936-1_18.
5
Asthma phenotyping: a necessity for improved therapeutic precision and new targeted therapies.哮喘表型分析:提高治疗精确性和新型靶向治疗的必要手段。
J Intern Med. 2016 Feb;279(2):192-204. doi: 10.1111/joim.12382. Epub 2015 Jun 15.
6
Neutrophilic Asthma and Potentially Related Target Therapies.中性粒细胞性哮喘与潜在相关的靶向治疗。
Curr Drug Targets. 2020;21(4):374-388. doi: 10.2174/1389450120666191011162526.
7
Aligning mouse models of asthma to human endotypes of disease.使哮喘小鼠模型与人类疾病内型相匹配。
Respirology. 2014 Aug;19(6):823-33. doi: 10.1111/resp.12315. Epub 2014 May 9.
8
Methods for Experimental Allergen Immunotherapy: Subcutaneous and Sublingual Desensitization in Mouse Models of Allergic Asthma.实验变应原免疫治疗方法:过敏性哮喘小鼠模型中的皮下和舌下脱敏。
Methods Mol Biol. 2021;2223:295-335. doi: 10.1007/978-1-0716-1001-5_20.
9
Inundation of asthma target research: Untangling asthma riddles.哮喘靶向研究热潮:解开哮喘谜团
Pulm Pharmacol Ther. 2016 Dec;41:60-85. doi: 10.1016/j.pupt.2016.09.010. Epub 2016 Sep 22.
10
Mitogen-activated protein kinases as therapeutic targets for asthma.丝裂原活化蛋白激酶作为哮喘的治疗靶点。
Pharmacol Ther. 2017 Jun;174:112-126. doi: 10.1016/j.pharmthera.2017.02.024. Epub 2017 Feb 14.

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