Aligning mouse models of asthma to human endotypes of disease.
Aligning mouse models of asthma to human endotypes of disease.
复制标题
将哮喘的小鼠模型与人类疾病的内型统一。
DOI：
10.1111/resp.12315
复制
发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Poynter ME
中科院分区：
文献类型：
--
作者：
Martin RA;Hodgkins SR;Dixon AE;Poynter ME
在理解哮喘的病理生理机制方面，利用临床前小鼠模型已经取得了实质性的进展。然而，由于哮喘是一种复杂的、异质性的综合征，很少是由单一过敏原引起的，而且通常是在没有特应性反应的情况下出现的，因此在小鼠模型上证明有效的有希望的疗法中，很少有转化为患者的新疗法。这导致迫切需要确定哮喘Th2低、非嗜酸性亚群的特征，研究对皮质类固醇等常规治疗具有抵抗力的模型，并开发针对严重疾病患者的治疗方法。根据潜在的病理生理机制对哮喘进行分类，称为内分型，为哮喘新疗法的开发提供了一种分层的方法。在临床前研究中，新的哮喘模型正在被利用，这些模型更接近于不同哮喘内型的临床特征，包括IL-17和Th17反应的存在，Th17反应是严重疾病的生物标志物。这些模型利用了更多与生理相关的致敏剂、加重因子和过敏原，并纳入了更好地反映临床哮喘的自然病史和慢性化的时间点。重要的是，一些模型更好地代表了非经典哮喘内型，这有助于研究非Th2驱动的病理，并类似于临床哮喘的复杂性质，包括皮质类固醇抵抗。将小鼠哮喘模型置于人类哮喘内型的背景下，将提供一种更相关的方法来理解疾病的病理生理机制，从而为那些仍然难以治疗的哮喘患者开发新的治疗方法。
Substantial gains in understanding the pathophysiologic mechanisms underlying asthma have been made using preclinical mouse models. However, because asthma is a complex, heterogeneous syndrome that is rarely due to a single allergen and that often presents in the absence of atopy, few of the promising therapeutics that demonstrated effectiveness in mouse models have translated into new treatments for patients. This has resulted in an urgent need to characterize Th2-low, noneosinophilic subsets of asthma, to study models that are resistant to conventional treatments such as corticosteroids, and to develop therapies targeting patients with severe disease. Classifying asthma based on underlying pathophysiologic mechanisms, known as endotyping, offers a stratified approach for the development of new therapies for asthma. In preclinical research, new models of asthma are being utilized that more closely resemble the clinical features of different asthma endotypes, including the presence of IL-17 and a Th17 response, a biomarker of severe disease. These models utilize more physiologically relevant sensitizing agents, exacerbating factors, and allergens, as well as incorporate time points that better reflect the natural history and chronicity of clinical asthma. Importantly, some models better represent nonclassical asthma endotypes that facilitate the study of non-Th2 driven pathology and resemble the complex nature of clinical asthma, including corticosteroid resistance. Placing mouse asthma models into the context of human asthma endotypes will afford a more relevant approach to the understanding of pathophysiological mechanisms of disease that will afford the development of new therapies for those asthmatics that remain difficult to treat.
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影响因子：
4.6
作者：
Ackerman, KG;Huang, HL;Beier, DR
通讯作者：
Beier, DR
DOI：
10.1096/fj.08-107979
发表时间：
2008-11
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Harrington LS;Lucas R;McMaster SK;Moreno L;Scadding G;Warner TD;Mitchell JA
通讯作者：
Mitchell JA
影响因子：
158.5
作者：
Corren, Jonathan;Lemanske, Robert F., Jr.;Matthews, John G.
通讯作者：
Matthews, John G.
影响因子：
9.1
作者：
Bleck, Bertram;Tse, Doris B.;Reibman, Joan
通讯作者：
Reibman, Joan
DOI：
10.1164/rccm.200711-1754oc
发表时间：
2008-08-01
影响因子：
24.7
作者：
Haldar P;Pavord ID;Shaw DE;Berry MA;Thomas M;Brightling CE;Wardlaw AJ;Green RH
通讯作者：
Green RH