Exacerbation of experimental allergic asthma by augmented Th2 responses in WSX-1-deficient mice
Exacerbation of experimental allergic asthma by augmented Th2 responses in WSX-1-deficient mice
复制标题
DOI：
10.4049/jimmunol.175.4.2401
复制
发表时间：
2005-08-15
影响因子：
4.4
通讯作者：
Yoshida, H
中科院分区：
文献类型：
--
作者：
Miyazaki, Y;Inoue, H;Yoshida, H
WSX-1（IL-27 R）是一种I类细胞因子受体，与gp 130和IL-12受体具有同源性，通常在CD 4（+）T淋巴细胞上表达。尽管先前的报道已经阐明IL-27/WSX-1信号传导在一些细菌或原生动物感染期间在Th 1分化和细胞活化的减弱以及促炎细胞因子产生中起关键作用，但关于WSX-1在由麻黄碱介导的过敏性疾病中的重要性知之甚少。为此，我们利用WSX-1缺陷（WSX-1（-/-））小鼠和诱导实验性哮喘，其中Th 2细胞因子是病理学的中央调节器。与野生型小鼠相比，OVA攻击的WSX-1（-/-）小鼠表现出明显的气道反应性增强，杯状细胞增生，肺嗜酸性粒细胞浸润，血清IgE水平升高。与野生型小鼠相比，WSX-1（-/-）小鼠肺或支气管周围淋巴结CD 4（+）T细胞培养上清液中Th 2细胞因子的产生增加，Th 2细胞因子是哮喘发病的主要原因。令人惊讶的是，IFN-γ的产生也在WSX-1（-/-）小鼠中增强，尽管浓度较低。因此，细胞因子的过度产生似乎独立于WSX-1的Th 1促进特性。这些结果表明，IL-27/WSX-1还通过其对细胞因子产生的抑制作用在变应性哮喘的发展过程中的气道高反应性和肺部炎症的下调中起重要作用。
WSX-1 (IL-27R) is a class I cytokine receptor with homology to gp130 and IL-12 receptors and is typically expressed on CD4(+) T lymphocytes. Although previous reports have clarified that IL-27/WSX-1 signaling plays critical roles in both Th1 differentiation and attenuation of cell activation and proinflammatory cytokine production during some bacterial or protozoan infections, little is known about the importance of WSX-1 in cytokine-mediated diseases of allergic origin. To this aim, we took advantage of WSX-1-deficient (WSX-1(-/-)) mice and induced experimental asthma, in which Th2 cytokines are central modulators of the pathology. OVA-challenged WSX-1(-/-) mice showed marked enhancement of airway responsiveness with goblet cell hyperplasia, pulmonary eosinophil infiltration, and increased serum IgE levels compared with wild-type mice. Production of Th2 cytokines, which are largely responsible for the pathogenesis of asthma, was augmented in the lung or in the culture supernatants of peribronchial lymph node CD4(+) T cells from WSX-1(-/-) mice compared with those from wild-type mice. Surprisingly, IFN-gamma production was also enhanced in WSX-1(-/-) mice, albeit at a low concentration. The cytokine overproduction, thus, seems independent from the Th1-promoting property of WSX-1. These results demonstrated that IL-27/WSX-1 also plays an important role in the down-regulation of airway hyper-reactivity and lung inflammation during the development of allergic asthma through its suppressive effect on cytokine production.