CCR4 is a key modulator of innate immune responses
CCR4 is a key modulator of innate immune responses
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DOI：
10.4049/jimmunol.177.11.7531
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发表时间：
2006-12-01
影响因子：
4.4
通讯作者：
Kunkel, Steven L.
中科院分区：
文献类型：
--
作者：
Ness, Traci L.;Ewing, Jillian L.;Kunkel, Steven L.
CCR 4被认为是Th 2相关免疫过程中的关键受体，尽管对其在先天免疫中的作用知之甚少。先前的研究报道了与野生型小鼠相比，CCR 4（-/-）小鼠对LPS诱导的致死性的抗性增加。这项研究表明，CCR 4（-/-）小鼠对其他TLR激动剂的攻击以及细菌性腹膜炎具有相似的抗性。耐药与早期白细胞募集增强、TLR表达增加、2型细胞因子/趋化因子谱偏斜以及细菌清除改善相关。来自CCR 4（-/-）小鼠的巨噬细胞表现出与交替激活一致的许多特征，包括2型细胞因子/趋化因子和在炎症区1（FIZZ 1）蛋白中发现的分泌增加。在CCR 4（-/-）巨噬细胞中，MyD 88依赖的NF-κ B信号转导显著下调，而p38 MAPK和JNK活化相反增加。这些数据强调了CCR 4在巨噬细胞分化和对病原体的先天免疫应答中的重要性，以及趋化因子受体表达参与TLR信号调节。免疫学杂志，2006，177：7531-7539.
CCR4 is recognized as a key receptor in Th2-associated immune processes, although very little is known about its role in innate immunity. Previous studies reported increased resistance to LPS-induced lethality in CCR4(-/-) mice compared with wild-type mice. This study demonstrates that CCR4(-/-) mice are similarly resistant to challenge with other TLR agonists, as well as bacterial peritonitis. Resistance was associated with enhanced early leukocyte recruitment, increased TLR expression, a skewed type 2 cytokine/chemokine profile, And improved bacterial clearance. Macrophages from CCR4(-/-) mice exhibited many features consistent with alternative activation, including elevated secretion of type 2 cytokines/chemokines and the found in inflammatory zone 1 (FIZZ1) protein. MyD88-dependent NF-kappa B signaling was significantly down-regulated in CCR4(-/-) macrophages, whereas p38 MAPK and JNK activation were conversely increased. These data stress the importance of CCR4 in macrophage differentiation and innate immune responses to pathogens, as well as the involvement of chemokine receptor expression in TLR signaling regulation. The Journal of Immunology, 2006, 177: 7531-7539.