Chensue S W, Lukacs N W, Yang T Y, Shang X, Frait K A, Kunkel S L, Kung T, Wiekowski M T, Hedrick J A, Cook D N, Zingoni A, Narula S K, Zlotnik A, Barrat F J, O'Garra A, Napolitano M, Lira S A
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48105, USA.
J Exp Med. 2001 Mar 5;193(5):573-84. doi: 10.1084/jem.193.5.573.
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.
趋化因子受体转导对白细胞功能和运输至关重要的信号。最近研究表明，CC趋化因子受体（CCR）8由Th2亚群选择性表达，但其功能相关性尚不清楚。为了阐明CCR8的生物学作用，我们培育了CCR8基因缺陷（-/-）小鼠。在此我们报告，在曼氏血吸虫可溶性虫卵抗原（SEA）诱导的肉芽肿形成模型以及卵清蛋白（OVA）和蟑螂抗原（CRA）诱导的过敏性气道炎症模型中，CCR8（-/-）小鼠体内的2型辅助性T细胞（Th2）免疫反应存在缺陷。在这些小鼠中，对SEA、OVA和CRA的反应显示Th2细胞因子产生受损，这与异常的2型炎症相关，嗜酸性粒细胞减少了50%至80%。相比之下，由牛分枝杆菌纯化蛋白衍生物（PPD）引发的典型Th1免疫反应不受CCR8缺陷的影响。机制分析表明，Th2细胞正常发育，嗜酸性粒细胞募集减少可能是由于白细胞介素5的全身性减少。这些结果表明CCR8在体内Th2功能反应中起重要作用。
