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首页> 外文期刊>The journal of immunology >Chemokine Receptor 4 Plays a Key Role in T Cell Recruitment into the Airways of Asthmatic Patients
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Chemokine Receptor 4 Plays a Key Role in T Cell Recruitment into the Airways of Asthmatic Patients

机译：趋化因子受体4在哮喘患者气道T细胞募集中起关键作用

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T lymphocytes of the Th2 type are central orchestrators of airway inflammation in asthma. The mechanisms that regulate their accumulation in the asthmatic airways remains poorly understood. We tested the hypothesis that CCR4, preferentially expressed on T lymphocytes of the Th2 type, plays a critical role in this process. We enumerated by flow cytometry the CCR4-expressing T cells from blood, induced sputum, and biopsy samples of patients with asthma and control subjects. We showed a positive correlation between the numbers of peripheral blood CCR4+ T cells and asthma severity, provided evidence of preferential accumulation of CCR4+ T cells in asthmatic airways, and demonstrated that CCR4+ but not CCR4? cells from patients with asthma produce Th2 cytokines. Explanted airway mucosal biopsy specimens, acquired by bronchoscopy from subjects with asthma, were challenged with allergen and the explant supernatants assayed for T cell chemotactic activity. Allergen-induced ex vivo production of the CCR4 ligand, CCL17 was raised in explants from patients with asthma when compared with healthy controls. Using chemotaxis assays, we showed that the T cell chemotactic activity generated by bronchial explants can be blocked with a selective CCR4 antagonist or by depleting CCR4+ cells from responder cells. These results provide evidence that CCR4 might play a role in allergen-driven Th2 cell accumulation in asthmatic airways. Targeting this chemokine receptor in patients with asthma might reduce Th2 cell-driven airway inflammation; therefore, CCR4 antagonists could be an effective new therapy for asthma. This study also provides wider proof of concept for using tissue explants to study immunomodulatory drugs for asthma.
机译：Th2型T淋巴细胞是哮喘气道炎症的主要协调器。调节其在哮喘气道中积累的机制仍知之甚少。我们检验了以下假设：CCR4在Th2型T淋巴细胞上优先表达，在此过程中起关键作用。我们通过流式细胞术从哮喘患者和对照组的血液，诱导的痰​​液和活检样本中计数了表达CCR4的T细胞。我们显示外周血CCR4 + T细胞的数量与哮喘严重程度之间呈正相关，提供了哮喘气道中CCR4 + T细胞优先积累的证据，并证明了CCR4 +但不是CCR4？来自哮喘患者的细胞会产生Th2细胞因子。通过支气管镜检查从哮喘患者中获取的气道黏膜活检标本，用过敏原攻击，并检测上清液的T细胞趋化活性。与健康对照相比，哮喘患者的外植体中变应原诱导的CCR4配体CCL17的体外产生增加。使用趋化性测定，我们显示了支气管外植体产生的T细胞趋化活性可以用选择性CCR4拮抗剂或从应答细胞中清除CCR4 +细胞来阻断。这些结果提供了证据，表明CCR4可能在哮喘气道中由变应原驱动的Th2细胞积聚中起作用。针对哮喘患者的这种趋化因子受体可以减少Th2细胞驱动的气道炎症。因此，CCR4拮抗剂可能是一种有效的哮喘新疗法。这项研究还为使用组织外植体研究哮喘免疫调节药物提供了更广泛的概念证明。

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