Université d'Orléans and CNRS, Molecular Immunology and Embryology (IEM), Orléans, France.
Allergy. 2011 Aug;66(8):1047-57. doi: 10.1111/j.1398-9995.2011.02586.x. Epub 2011 Mar 28.
Inflammasome activation with the production of IL-1β received substantial attention recently in inflammatory diseases. However, the role of inflammasome in the pathogenesis of asthma is not clear. Using an adjuvant-free model of allergic lung inflammation induced by ovalbumin (OVA), we investigated the role of NLRP3 inflammasome and related it to IL-1R1 signaling pathway.
Allergic lung inflammation induced by OVA was evaluated in vivo in mice deficient in NLRP3 inflammasome, IL-1R1, IL-1β or IL-1α. Eosinophil recruitment, Th2 cytokine, and chemokine levels were determined in bronchoalveolar lavage fluid, lung homogenates, and mediastinal lymph node cells ex vivo.
Allergic airway inflammation depends on NLRP3 inflammasome activation. Dendritic cell recruitment into lymph nodes, Th2 lymphocyte activation in the lung and secretion of Th2 cytokines and chemokines are reduced in the absence of NLRP3. Absence of NLRP3 and IL-1β is associated with reduced expression of other proinflammatory cytokines such as IL-5, IL-13, IL-33, and thymic stromal lymphopoietin. Furthermore, the critical role of IL-1R1 signaling in allergic inflammation is confirmed in IL-1R1-, IL-1β-, and IL-1α-deficient mice.
NLRP3 inflammasome activation leading to IL-1 production is critical for the induction of a Th2 inflammatory allergic response.
最近，白细胞介素-1β（IL-1β）产生的炎症小体激活在炎症性疾病中受到了广泛关注。然而，炎症小体在哮喘发病机制中的作用尚不清楚。本研究使用卵清蛋白（OVA）诱导的无佐剂过敏肺炎症模型，研究了 NOD 样受体热蛋白结构域 3（NLRP3）炎症小体的作用，并将其与白细胞介素-1 受体 1（IL-1R1）信号通路相关联。
在 NLRP3 炎症小体、IL-1R1、IL-1β或 IL-1α 缺失的小鼠中，体内评估 OVA 诱导的过敏肺炎症。在体外，通过支气管肺泡灌洗、肺匀浆和纵隔淋巴结细胞测定嗜酸性粒细胞募集、Th2 细胞因子和趋化因子水平。
过敏气道炎症依赖于 NLRP3 炎症小体的激活。树突状细胞向淋巴结的募集、肺内 Th2 淋巴细胞的激活以及 Th2 细胞因子和趋化因子的分泌在 NLRP3 缺失的情况下减少。NLRP3 和 IL-1β 的缺失与其他促炎细胞因子（如 IL-5、IL-13、IL-33 和胸腺基质淋巴生成素）的表达减少有关。此外，在 IL-1R1、IL-1β 和 IL-1α 缺失的小鼠中证实了 IL-1R1 信号在过敏炎症中的关键作用。
导致 IL-1 产生的 NLRP3 炎症小体的激活对于诱导 Th2 炎症性过敏反应是至关重要的。
