IL-25 and IL-33 Contribute to Development of Eosinophilic Airway Inflammation in Epicutaneously Antigen-Sensitized Mice.
IL-25 and IL-33 Contribute to Development of Eosinophilic Airway Inflammation in Epicutaneously Antigen-Sensitized Mice.
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DOI：
10.1371/journal.pone.0134226
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Nakae S
中科院分区：
文献类型：
--
作者：
Morita H;Arae K;Unno H;Toyama S;Motomura K;Matsuda A;Suto H;Okumura K;Sudo K;Takahashi T;Saito H;Matsumoto K;Nakae S
IL-25、IL-33和TSLP主要由上皮细胞产生，并且已知诱导Th 2型细胞因子。Th 2型细胞因子不仅参与宿主对线虫的防御，而且参与Th 2型变态反应性疾病的发展。据报道，TSLP对小鼠吸入过敏原后过敏性气道炎症的发展至关重要，这些过敏原事先已被致敏的上皮细胞（EC）。然而，IL-25和IL-33在环境中的作用仍不清楚。用卵清蛋白（OVA）致敏IL-25和IL-33缺陷的小鼠EC，然后用OVA鼻内攻击。分别通过组织学分析、血细胞计数器和带呼吸机的体积描记器测定小鼠气道炎症、支气管肺泡灌洗液（BALF）中炎性细胞数量和气道高反应性（AHR）。采用定量PCR法检测皮肤和肺组织中mRNA的表达，ELISA法检测BALF中髓过氧化物酶（MPO）和嗜酸性粒细胞过氧化物酶（EPO）的含量及血清IgE水平。 在用OVA致敏EC后，在IL-25缺陷（IL-25-/-）和IL-33-/-小鼠中观察到淋巴结和脾脏的正常OVA特异性Th 2-和Th 17-细胞应答。然而，在用OVA预致敏EC的IL-25-/-和IL-33-/-小鼠中，BALF中嗜酸性粒细胞的数量而不是中性粒细胞的数量，以及肺中Th 2细胞因子的水平而不是Th 17细胞因子的水平显著降低，而它们的AHR和OVA特异性血清IgE的水平是正常的。IL-25和IL-33在OVA致敏EC小鼠激发期肺局部诱导Th 2型丝氨酸介导的过敏性气道嗜酸性粒细胞增多症，而不是Th 17型丝氨酸介导的气道嗜酸性粒细胞增多症中起关键作用。它们不影响致敏阶段的OVA特异性T细胞诱导。
IL-25, IL-33 and TSLP are produced predominantly by epithelial cells and are known to induce Th2-type cytokines. Th2-type cytokines are involved not only in host defense against nematodes, but also in the development of Th2-type allergic diseases. TSLP was reported to be crucial for development of allergic airway inflammation in mice after inhalation of allergens to which they had been sensitized epicutaneously (EC) beforehand. However, the roles of IL-25 and IL-33 in the setting remain unclear. Mice deficient in IL-25 and IL-33 were sensitized EC with ovalbumin (OVA) and then challenged intranasally with OVA. Airway inflammation, the number of inflammatory cells in bronchoalveolar lavage fluids (BALFs) and airway hyperresponsiveness (AHR) in the mice were determined, respectively, by histological analysis, with a hemocytometer, and by using plethysmograph chambers with a ventilator. Expression of mRNA in the skin and lungs was determined by quantitative PCR, while the BALF levels of myeloperoxidase (MPO) and eosinophil peroxidase (EPO) and the serum levels of IgE were determined by ELISA. Normal OVA-specific Th2- and Th17-cell responses of lymph nodes and spleens were observed in IL-25-deficient (IL-25-/-) and IL-33-/- mice after EC sensitization with OVA. Nevertheless, the number of eosinophils, but not neutrophils, in the BALFs, and the levels of Th2 cytokines, but not Th17 cytokines, in the lungs were significantly decreased in the IL-25-/- and IL-33-/- mice pre-sensitized EC with OVA, followed by inhalation of OVA, whereas their levels of AHR and OVA-specific serum IgE were normal. Both IL-25 and IL-33 are critical for induction of Th2-type cytokine-mediated allergic airway eosinophilia, but not Th17-type cytokine-mediated airway neutrophilia, at the local sites of lungs in the challenge phase of mice sensitized EC with OVA. They do not affect OVA-specific T-cell induction in the sensitization phase.