United airways: circulating Th2 effector cells in an allergic rhinitis model are responsible for promoting lower airways inflammation
United airways: circulating Th2 effector cells in an allergic rhinitis model are responsible for promoting lower airways inflammation
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DOI：
10.1111/j.1365-2222.2009.03417.x
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发表时间：
2010-03-01
影响因子：
6.1
通讯作者：
Lambrecht, B. N.
中科院分区：
文献类型：
--
作者：
KleinJan, A.;Willart, M.;Lambrecht, B. N.
变应性鼻炎（AR）和哮喘经常共存，被称为“联合气道”疾病。然而，参与上、下气道相互作用的关键分子和细胞途径仍有待确定。目的：我们试图评估过敏性鼻炎是否以及如何在过敏原攻击下加剧小鼠下气道炎症。方法我们建立了鼻内卵清蛋白（OVA）驱动的AR模型，其特征是鼻腔嗜酸性粒细胞炎症，增高血清OVA特异性IgE水平和颈部淋巴结Th2细胞因子的产生。对ova致敏小鼠，不论有无AR，均给予下气道刺激，24 h后分析下气道炎症。结果我们发现，与OVA致敏的对照组相比，AR小鼠在低气道OVA攻击后更容易发生嗜酸性粒细胞炎症。与ova致敏对照组相比，AR小鼠支气管肺泡灌洗液中嗜酸性粒细胞数量增加，肺内皮细胞间粘附分子-1 （ICAM-1）表达增加。在ova挑战的AR小鼠中，T细胞的消耗完全消除了下气道炎症的所有标志，包括IL-5和组织嗜酸性粒细胞的增强。相反，在初始动物中过继转移Th2效应细胞可诱导OVA攻击后下气道嗜酸性粒细胞炎症。自旋腺苷-1类似物FTY720在AR发育过程中阻断T细胞再循环，也可以防止AR小鼠在单次下气道刺激下的下气道炎症，包括ICAM-1的表达。结论我们的“联合气道”疾病小鼠模型支持流行病学和临床数据，即AR对下气道炎症有显著影响。循环Th2效应细胞负责AR小鼠的肺启动，最有可能是通过上调ICAM-1。引用本文：A. KleinJan， M. Willart， M. van Nimwegen， K. Leman， H. C. Hoogsteden， R.W. Hendriks， B.N. Lambrecht，临床与实验过敏，2010(40)494-504。
P>BackgroundAllergic rhinitis (AR) and asthma often coexist and are referred to as 'united airways' disease. However, the molecular and cellular pathways that are crucially involved in the interaction between upper and lower airways remain to be identified.ObjectiveWe sought to assess whether and how AR exacerbates lower airway inflammation upon allergen challenge in mice.MethodsWe previously developed an intranasal ovalbumin (OVA)-driven AR model, characterized by nasal eosinophilic inflammation, enhanced serum levels of OVA-specific IgE and Th2 cytokine production in cervical lymph nodes. In OVA-sensitized mice with or without AR, a lower airway challenge was given, and after 24 h, lower airway inflammation was analysed.ResultsWe found that AR mice were more susceptible to eosinophilic inflammation following a lower airway OVA challenge than OVA-sensitized controls. AR mice manifested increased numbers of eosinophils in bronchoalveolar lavage fluid and increased inter-cellular adhesion molecule-1 (ICAM-1) expression on lung endothelium, when compared with OVA-sensitized controls. Depletion of T cells in OVA-challenged AR mice completely abrogated all hallmarks of lower airway inflammation, including enhanced IL-5 and tissue eosinophilia. Conversely, adoptive transfer of Th2 effector cells in naive animals induced lower airway eosinophilic inflammation after challenge with OVA. Blocking T cell recirculation during AR development by the spingosine-1 analogue FTY720 also prevented lower airway inflammation including ICAM-1 expression in AR mice upon a single lower airway challenge.ConclusionOur mouse model of 'united airways' disease supports epidemiological and clinical data that AR has a significant impact on lower airway inflammation. Circulating Th2 effector cells are responsible for lung priming in AR mice, most likely through up-regulation of ICAM-1.Cite this as: A. KleinJan, M. Willart, M. van Nimwegen, K. Leman, H. C. Hoogsteden, R.W. Hendriks and B.N. Lambrecht, Clinical & Experimental Allergy, 2010 (40) 494-504.