Natural killer T cells contribute to airway eosinophilic inflammation induced by ragweed through enhanced IL-4 and eotaxin production
Natural killer T cells contribute to airway eosinophilic inflammation induced by ragweed through enhanced IL-4 and eotaxin production
复制标题
DOI：
10.1002/eji.200324303
复制
发表时间：
2004-02-01
影响因子：
5.4
通讯作者：
Yang, X
中科院分区：
文献类型：
--
作者：
Bilenki, L;Yang, J;Yang, X
尽管已经发现NKT细胞能够在几种模型系统中调节免疫应答，但NKT细胞在变态反应中的作用仍不清楚。使用缺乏NKT细胞的CD 1基因敲除（KO）小鼠，我们研究了NKT细胞在由常见的空气传播的人类过敏原豚草诱导的过敏性炎症发展中的功能。数据显示，由豚草诱导的气道嗜酸性粒细胞增多和粘液过度产生在CD 1 KO小鼠中显著减少，这与CD 1 KO小鼠气道中显著较低的变应原驱动的IL-4产生和较低的嗜酸性粒细胞趋化因子应答相关。此外，豚草特异性和总血清IgE水平在CD 1 KO小鼠显着低于对照BALB/c小鼠。CD 1 KO小鼠的过敏反应降低不是由于内在缺陷，因为它们表现出正常的免疫细胞和功能水平。此外，在体内刺激NKT细胞使用其天然配体，α-半乳糖神经酰胺，增强豚草诱导的气道嗜酸性粒细胞增多症，IL-4，嗜酸性粒细胞活化趋化因子的生产在控制，但不是CD 1 KO小鼠。这些数据为NKT细胞参与过敏原驱动的细胞因子和趋化因子产生和气道炎症的过敏机制提供了体内证据。
Although NKT cells have been found to be capable of modulating immune responses in several model systems, the role of NKT cells in allergy remains unclear. Using CD1 gene knockout (KO) mice, which lack NKT cells, we examined the function of NKT cells in the development of allergic inflammation induced by a common airborne human allergen, ragweed. The data showed that airway eosinophilia and mucus overproduction induced by ragweed were significantly reduced in CD1 KO mice, which was correlated with significantly lower allergen-driven IL-4 production and lower eotaxin responses in the airways of CD1 KO mice. Moreover, both ragweed-specific and total serum IgE levels in CD1 KO mice were significantly lower than those in control BALB/c mice. The reduced allergic reaction in CD1 KO mice is not due to intrinsic deficiency because they showed normal levels of immune cells and function. In addition, in vivo stimulation of NKT cells using their natural ligand, alpha-galactosylceramide, enhanced ragweed-induced airway eosinophilia, IL-4, and eotaxin production in control, but not CD1 KO mice. These data provide in vivo evidence for the involvement of NKT cells in the allergic mechanisms responsible for allergen-driven cytokine and chemokine production and airway inflammation.