IL-23 and Th17 Cells Enhance Th2-Cell-mediated Eosinophilic Airway Inflammation in Mice
IL-23 and Th17 Cells Enhance Th2-Cell-mediated Eosinophilic Airway Inflammation in Mice
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DOI：
10.1164/rccm.200801-086oc
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发表时间：
2008-11-15
影响因子：
24.7
通讯作者：
Nakajima, Hiroshi
中科院分区：
文献类型：
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作者：
Wakashin, Hidefumi;Hirose, Koichi;Nakajima, Hiroshi
产生IL-23-IL-17 A的CD 4（+）T细胞（Th 17细胞）轴在慢性炎症性疾病（包括自身免疫性疾病）的发展中起重要作用。然而，IL-23-Th 17细胞轴在过敏性气道炎症的调节中的作用在很大程度上仍然是未知的。目的：确定IL-23和Th 17细胞在过敏性气道炎症中的作用。方法：我们检测了抗IL-23抗体对抗原诱导的气道炎症的影响。我们还通过产生肺特异性IL-23转基因小鼠来研究IL-23的增强表达对过敏性气道炎症的影响。此外，我们研究了过继转移的抗原特异性Th 17细胞对过敏性气道inflammation. Measures和主要结果的影响：IL-23的mRNA表达在致敏小鼠抗原吸入后的肺，中和IL-23减少抗原诱导的嗜酸性粒细胞的招聘和Th 2细胞因子的产生在气道。气道中IL-23的强制表达显著增强了抗原诱导的嗜酸性粒细胞和中性粒细胞向气道中的募集;气道中Th 2细胞因子、IL-17 A和肿瘤坏死因子（TNF）-α的产生;杯状细胞增生;以及气道高反应性。此外，在缺乏IL-17 A的小鼠中仍然观察到IL-23介导的抗原诱导的Th 2细胞因子产生和气道中嗜酸性粒细胞募集的增强。此外，尽管抗原特异性Th 17细胞单独过继转移诱导中性粒细胞而不是嗜酸性粒细胞在抗原吸入后募集到气道中，但Th 17细胞与Th 2细胞的共转移显著增强抗原诱导的Th 2细胞介导的嗜酸性粒细胞募集到气道中和气道高反应性。IL-23和Th 17细胞不仅诱导Th 17细胞介导的嗜酸性气道炎症，而且上调Th 2细胞介导的嗜酸性气道炎症。
Rationale The IL-23-IL-17A-producing CD4(+) T-cell (Th17 cell) axis plays an important role in the development of chronic inflammatory diseases, including autoimmune diseases. However, the role of the IL-23-Th17 cell axis in the regulation of allergic airway inflammation is still largely unknown.Objectives: To determine the role of IL-23 and Th17 cells in allergic airway inflammation.Methods: We examined the effect of anti-IL-23 antibody on antigen-induced airway inflammation. We also investigated the effect of enforced expression of IL-23 on allergic airway inflammation by generating lung-specific IL-23 transgenic mice. Moreover, we examined the effect of adoptive transfer of antigen-specific Th17 cells on allergic airway inflammation.Measurements and Main Results: IL-23 mRNA was expressed in the lung of sensitized mice upon antigen inhalation, and the neutralization of IL-23 decreased antigen-induced eosinophil recruitment and Th2 cytokine production in the airways. The enforced expression of IL-23 in the airways significantly enhanced antigen-induced eosinophil and neutrophil recruitment into the airways; Th2 cytokine, IL-17A, and tumor necrosis factor (TNF)-alpha production in the airways; goblet cell hyperplasia; and airway hyperresponsiveness. Moreover, IL-23-mediated enhancement of antigen-induced Th2 cytokine production and eosinophil recruitment in the airways was still observed in the mice lacking IL-17A. Furthermore, although adoptive transfer of antigen-specific Th17 cells alone induced neutrophil but not eosinophil recruitment into the airways upon antigen inhalation, cotransfer of Th17 cells with Th2 cells significantly enhanced antigen-induced Th2-cell-mediated eosinophil recruitment into the airways and airway hyperresponsiveiness.Conclusions: IL-23 and Th17 cells not only induce Th17-cell-mediated neutrophilic airway inflammation but also up-regulate Th2-cell-mediated eosinophilic airway inflammation.