Aberrant in vivo T helper type 2 cell response and impaired eosinophil recruitment in CC chemokine receptor 8 knockout mice.
Aberrant in vivo T helper type 2 cell response and impaired eosinophil recruitment in CC chemokine receptor 8 knockout mice.
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DOI：
10.1084/jem.193.5.573
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发表时间：
2001-03-05
期刊：
影响因子：
--
通讯作者：
Lira SA
中科院分区：
文献类型：
--
作者：
Chensue SW;Lukacs NW;Yang TY;Shang X;Frait KA;Kunkel SL;Kung T;Wiekowski MT;Hedrick JA;Cook DN;Zingoni A;Narula SK;Zlotnik A;Barrat FJ;O'Garra A;Napolitano M;Lira SA
趋化因子受体是白细胞功能和运输的重要信号。最近，研究表明CC趋化因子受体（CCR）8选择性地由Th 2亚群表达，但其功能相关性尚不清楚。为了解决CCR 8的生物学作用，我们产生了CCR 8缺陷（−/−）小鼠。在这里，我们报告了CCR 8 −/−小鼠在曼氏血吸虫可溶性虫卵抗原（SEA）诱导的肉芽肿形成以及卵清蛋白（OVA）和蟑螂抗原（CRA）诱导的过敏性气道炎症模型中的体内辅助性T细胞2型（Th 2）免疫应答缺陷。在这些小鼠中，对SEA、OVA和CRA的反应显示与异常2型炎症相关的Th 2细胞因子产生受损，显示嗜酸性粒细胞减少50 - 80%。与此相反，原型Th 1免疫反应，引起的牛分枝杆菌纯化蛋白衍生物（PPD）不受CCR 8缺陷。机制分析表明，Th 2细胞发育正常，嗜酸性粒细胞募集减少可能是由于全身白细胞介素5减少。这些结果表明CCR 8在体内Th 2功能应答中具有重要作用。
Chemokine receptors transduce signals important for the function and trafficking of leukocytes. Recently, it has been shown that CC chemokine receptor (CCR)8 is selectively expressed by Th2 subsets, but its functional relevance is unclear. To address the biological role of CCR8, we generated CCR8 deficient (−/−) mice. Here we report defective T helper type 2 (Th2) immune responses in vivo in CCR8−/− mice in models of Schistosoma mansoni soluble egg antigen (SEA)-induced granuloma formation as well as ovalbumin (OVA)- and cockroach antigen (CRA)-induced allergic airway inflammation. In these mice, the response to SEA, OVA, and CRA showed impaired Th2 cytokine production that was associated with aberrant type 2 inflammation displaying a 50 to 80% reduction in eosinophils. In contrast, a prototypical Th1 immune response, elicited by Mycobacteria bovis purified protein derivative (PPD) was unaffected by CCR8 deficiency. Mechanistic analyses indicated that Th2 cells developed normally and that the reduction in eosinophil recruitment was likely due to systemic reduction in interleukin 5. These results indicate an important role for CCR8 in Th2 functional responses in vivo.
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DOI：
10.1084/jem.191.2.265
发表时间：
2000-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lloyd CM;Delaney T;Nguyen T;Tian J;Martinez-A C;Coyle AJ;Gutierrez-Ramos JC
通讯作者：
Gutierrez-Ramos JC
影响因子：
4.4
作者：
Metz, DP;Bottomly, K
通讯作者：
Bottomly, K
影响因子：
15.3
作者：
Endres, MJ;Garlisi, CG;Hedrick, JA
通讯作者：
Hedrick, JA
影响因子：
2.8
作者：
KUNG, TT;JONES, H;WATNICK, AS
通讯作者：
WATNICK, AS
影响因子：
15.3
作者：
Bonecchi, R;Bianchi, G;Bordignon, P P;D'Ambrosio, D;Lang, R;Borsatti, A;Sozzani, S;Allavena, P;Gray, P A;Mantovani, A;Sinigaglia, F
通讯作者：
Sinigaglia, F