Intervention of thymus and activation-regulated chemokine attenuates the development of allergic airway inflammation and hyperresponsiveness in mice
Intervention of thymus and activation-regulated chemokine attenuates the development of allergic airway inflammation and hyperresponsiveness in mice
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DOI：
10.4049/jimmunol.166.3.2055
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发表时间：
2001-02-01
影响因子：
4.4
通讯作者：
Matsushima, K
中科院分区：
文献类型：
--
作者：
Kawasaki, S;Takizawa, H;Matsushima, K
趋化因子和活化调节趋化因子（TARC; CCL 17）是一种淋巴细胞导向的CC趋化因子，特异性化学吸引CC趋化因子受体4阳性（CCR 4（+））Th 2细胞。为了建立TARC在体内的病理生理作用，我们在此研究了抗TARC的mAb是否可以抑制由OVA引起的小鼠哮喘反应的诱导，TARC在肺中组成性表达并且在过敏性炎症中上调。抗TARC的特异性抗体减弱了OVA诱导的气道嗜酸性粒细胞增多症，降低了气道高反应性的程度，同时降低了Th 2细胞因子水平。我们的研究结果首次表明，TARC是一个关键的趋化因子的发展Th 2为主的实验性过敏原诱导的哮喘与嗜酸性粒细胞增多症和AHR。这项研究也代表了通过靶向趋化因子在体内控制Th 2细胞因子产生的第一次成功。
Thymus- and activation-regulated chemokine (TARC; CCL17) is a lymphocyte-directed CC chemokine that specifically chemoattracts CC chemokine receptor 4-positive (CCR4(+)) Th2 cells. To establish the pathophysiological roles of TARC in vivo, we investigated here whether an mAb against TARC could inhibit the induction of asthmatic reaction in mice elicited by OVA, TARC was constitutively expressed in the lung and was up-regulated in allergic inflammation. The specific Ab against TARC attenuated OVA-induced airway eosinophilia and diminished the degree of airway hyperresponsiveness with a concomitant decrease in Th2 cytokine levels. Our results for the first time indicate that TARC is a pivotal chemokine for the development of Th2-dominated experimental allergen-induced asthma with eosinophilia and AHR. This study also represents the first success in controlling Th2 cytokine production in vivo by targeting a chemokine.