Th9 cells elicit eosinophil-independent bronchial hyperresponsiveness in mice
Th9 cells elicit eosinophil-independent bronchial hyperresponsiveness in mice
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DOI：
10.1016/j.alit.2016.05.003
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发表时间：
2016-09-01
影响因子：
6.8
通讯作者：
Hiroi, Takachika
中科院分区：
文献类型：
--
作者：
Saeki, Mayumi;Kaminuma, Osamu;Hiroi, Takachika
背景资料：嗜酸性粒细胞在气道的聚集和支气管高反应性（BHR）是支气管哮喘的显著特征，尽管嗜酸性粒细胞在BHR发生发展中的作用存在争议。与Th 2细胞介导的病理学类似，以IL-9产生活性为特征的Th 9细胞已被证明可诱导气道嗜酸性粒细胞增多症和BHR。本研究采用Th 9细胞介导的小鼠气道炎症模型，探讨嗜酸性粒细胞在Th 9介导的BHR中的作用。方法：体外从DO11.10/RAG-2（-/-）小鼠的CD 4（+）T细胞中诱导分化出卵清蛋白（OVA）特异性的Th 2和Th 9细胞，并检测这些细胞产生精氨酸的活性。用Th 2或Th 9细胞过继转移BALB/c小鼠，并用OVA攻击。结果：Th 2和Th 9细胞转移小鼠肺内嗜酸性粒细胞大量聚集，特异性抗原激发后可引起BHR。然而，一个基本的和嗜酸性粒细胞在Th 2和Th 9介导的BHR，分别证明了通过采用嗜酸性粒细胞缺陷小鼠的作用。供体细胞中IL-9的中和以及IL-10的缺乏并不影响Th 9介导的BHR。结论：与Th 2介导的和嗜酸性粒细胞依赖的BHR相反，Th 9可以独立于嗜酸性粒细胞及其特征性细胞因子IL-9和IL-10诱导BHR。Copyright（c）2016，Japanese Society of Allergology.制作和主办：Elsevier B. V.
Background: Airway accumulation of eosinophils and bronchial hyperresponsiveness (BHR) are prominent features of bronchial asthma, though the contribution of eosinophils to the development of BHR is controversial. Similar to Th2 cell-mediated pathology, Th9 cells, characterized by IL-9-producing activity, have been demonstrated to induce airway eosinophilia and BHR. In this study, we investigated the role of eosinophils in Th9-mediated BHR by employing Th9 cell-transferred murine airway inflammation model.Methods: Ovalbumin (OVA)-specific Th2 and Th9 cells were differentiated from CD4(+) T cells of DO11.10/RAG-2(-/-) mice in vitro and cytokine-producing activity of those cells was examined. BALB/c mice were adoptively transferred with Th2 or Th9 cells and challenged with OVA. Then, the number of inflammatory cells in bronchoalveolar lavage fluid and bronchial responsiveness to inhaled methacholine were determined.Results: Both in Th2 and Th9 cell-transferred mice, substantial accumulation of eosinophils in the lungs and BHR were induced by challenge with specific antigen. Nevertheless, an essential and dispensable role of eosinophils in Th2- and Th9-mediated BHR, respectively, was demonstrated by employing eosinophil-deficient mice. The neutralization of IL-9 as well as deficiency of IL-10 in the donor cells did not affect Th9-mediated BHR.Conclusions: In contrast to Th2-mediated and eosinophil-dependent BHR, Th9 could induce BHR independently from eosinophils and its characteristic cytokines, IL-9 and IL-10. Copyright (c) 2016, Japanese Society of Allergology. Production and hosting by Elsevier B.V.