Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17.
Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17.
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DOI：
10.1084/jem.20071507
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发表时间：
2008-02-18
期刊：
影响因子：
--
通讯作者：
Umetsu DT
中科院分区：
文献类型：
--
作者：
Pichavant M;Goya S;Meyer EH;Johnston RA;Kim HY;Matangkasombut P;Zhu M;Iwakura Y;Savage PB;DeKruyff RH;Shore SA;Umetsu DT
臭氧是空气污染的主要成分之一，暴露于臭氧会诱发一种在缺乏适应性免疫的情况下发生的哮喘。尽管臭氧诱发的哮喘以气道中性粒细胞增多而非嗜酸性粒细胞增多为特征，但它仍然与气道高反应性（AHR）相关，而气道高反应性是哮喘的一个主要特征。由于变应原诱发的AHR需要自然杀伤T（NKT）细胞的存在，我们询问臭氧诱发的AHR是否有类似的要求。我们发现野生型（WT）小鼠反复暴露于臭氧会诱发严重的AHR，同时伴有气道NKT细胞、中性粒细胞和巨噬细胞的增加。令人惊讶的是，NKT细胞缺陷型（CD1d - / - 和Jα18 - / - ）小鼠未能出现臭氧诱发的AHR。此外，用抗CD1d单克隆抗体处理WT小鼠可阻断NKT细胞的激活并预防臭氧诱发的AHR。而且，臭氧诱发的（而非变应原诱发的）AHR与产生白细胞介素（IL）-17的NKT细胞相关，并且在IL - 17 - / - 小鼠以及用抗IL - 17单克隆抗体处理的WT小鼠中不会发生。因此，臭氧暴露诱发的AHR需要NKT细胞的存在以及IL - 17的产生。由于NKT细胞是两种截然不同形式的AHR（臭氧诱发的和变应原诱发的）发展所必需的，我们的结果强烈表明NKT细胞介导了几种不同形式哮喘的统一致病机制，并且是有效哮喘治疗的一个独特靶点。
Exposure to ozone, which is a major component of air pollution, induces a form of asthma that occurs in the absence of adaptive immunity. Although ozone-induced asthma is characterized by airway neutrophilia, and not eosinophilia, it is nevertheless associated with airway hyperreactivity (AHR), which is a cardinal feature of asthma. Because AHR induced by allergens requires the presence of natural killer T (NKT) cells, we asked whether ozone-induced AHR had similar requirements. We found that repeated exposure of wild-type (WT) mice to ozone induced severe AHR associated with an increase in airway NKT cells, neutrophils, and macrophages. Surprisingly, NKT cell–deficient (CD1d−/− and Jα18−/−) mice failed to develop ozone-induced AHR. Further, treatment of WT mice with an anti-CD1d mAb blocked NKT cell activation and prevented ozone-induced AHR. Moreover, ozone-induced, but not allergen-induced, AHR was associated with NKT cells producing interleukin (IL)-17, and failed to occur in IL-17−/− mice nor in WT mice treated with anti–IL-17 mAb. Thus, ozone exposure induces AHR that requires the presence of NKT cells and IL-17 production. Because NKT cells are required for the development of two very disparate forms of AHR (ozone- and allergen-induced), our results strongly suggest that NKT cells mediate a unifying pathogenic mechanism for several distinct forms of asthma, and represent a unique target for effective asthma therapy.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
4.6
作者：
Hamzaoui, Agnes;Rouhou, Sana Cheik;Hamzaoui, Kamel
通讯作者：
Hamzaoui, Kamel
DOI：
10.1016/j.biocel.2004.11.019
发表时间：
2005-07-01
影响因子：
4
作者：
Mercer, JC;Ragin, MJ;August, A
通讯作者：
August, A
影响因子：
4.4
作者：
Li, N;Alam, J;Nel, AE
通讯作者：
Nel, AE
影响因子：
9.6
作者：
Gibson, PG;Simpson, JL;Saltos, N
通讯作者：
Saltos, N