BACKGROUND Mouse models have been extremely valuable in identifying the fundamental mechanisms of airway inflammation that underlie human allergic asthma. Several models are commonly used, employing different methods and routes of sensitisation, and allergens of varying clinical relevance. Although all models elicit similar hallmarks of allergic airway inflammation, including airway eosinophilia, goblet cell hyperplasia and cellular infiltration in lung, it is not established whether they do so by involving the same mechanisms. RESULTS We compared the impact of inactivation of various innate or adaptive immune genes, as well as sex, in different models of allergic airway inflammation in mice of C57BL/6 background. Chicken ovalbumin (OVA) and house dust mite (HDM) were used as allergens in settings of single or multiple intranasal (i.n.) challenges, after sensitisation in adjuvant or in adjuvant-free conditions. Eosinophil numbers in the broncho-alveolar lavage and lung histopathology were assessed in each model. We found that Major Histocompatibility Complex Class II (MHCII) deficiency and lack of conventional CD4+ T cells had the most profound effect, essentially ablating airway eosinophilia and goblet cell hyperplasia in all models. In contrast, Thymic stromal lymphopoietin receptor (TSLPR) deficiency greatly reduced eosinophilia but had a variable effect on goblet cells. CD1d deficiency and lack of Natural Killer T (NKT) cells moderately impaired inflammation in OVA models but not HDM, whereas sex affected the response to HDM but not OVA. Lastly, defective Toll-like receptor (TLR)4 expression had only a relatively modest overall impact on inflammation. CONCLUSION All the models studied were comparably dependent on adaptive CD4+ T cell responses and TSLP. In contrast, sex, NKT cells and TLR4 appeared to play subtler and more variable roles that were dependent on the type of allergen and mode of immunization and challenge. These results are consistent with clinical data suggesting a key role of CD4+ T cells and TSLP in patients with allergic asthma.

中文翻译：

---

类似的免疫机制可控制由不同的过敏原和治疗方案引起的实验性气道嗜酸性粒细胞增多。

背景技术小鼠模型对于鉴定人类过敏性哮喘的气道炎症的基本机制具有极其重要的价值。通常使用几种模型，它们采用不同的致敏方法和途径，以及具有不同临床相关性的过敏原。尽管所有模型都具有类似的过敏性气道炎症标志，包括气道嗜酸性粒细胞增多症，杯状细胞增生和肺部细胞浸润，但尚不清楚它们是否通过涉及相同的机制来做到这一点。结果我们比较了不同先天性或适应性免疫基因失活以及性别对C57BL / 6背景小鼠过敏性气道炎症模型的影响。鸡卵白蛋白（OVA）和屋尘螨（HDM）用作单鼻或多鼻内（在鼻内）的变应原 ）在佐剂或无佐剂条件下致敏后的挑战。在每个模型中评估了支气管肺泡灌洗中的嗜酸性粒细胞数量和肺组织病理学。我们发现，II型主要组织相容性复合体（MHCII）缺乏和缺乏常规CD4 + T细胞具有最深远的影响，在所有模型中均基本消除了气道嗜酸性粒细胞增多和杯状细胞增生。相比之下，胸腺基质淋巴细胞生成素受体（TSLPR）的缺乏大大降低了嗜酸性粒细胞增多，但对杯状细胞的作用却有所不同。CD1d缺乏和缺乏天然杀伤性T细胞（NKT）会在OVA模型中减轻炎症，但不会损害HDM，而性别会影响对HDM的反应，但不会影响OVA。最后，有缺陷的Toll样受体（TLR）4表达对炎症的影响相对较小。结论所有研究的模型都相当依赖于适应性CD4 + T细胞反应和TSLP。相比之下，性别，NKT细胞和TLR4似乎起着更微妙和更多可变的作用，这取决于过敏原的类型以及免疫和攻击的方式。这些结果与临床数据一致，表明CD4 + T细胞和TSLP在过敏性哮喘患者中起关键作用。