Association of a new-type prostaglandin D2 receptor CRTH2 with circulating T helper 2 cells in patients with atopic dermatitis
Association of a new-type prostaglandin D2 receptor CRTH2 with circulating T helper 2 cells in patients with atopic dermatitis
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DOI：
10.1046/j.1523-1747.2002.01862.x
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发表时间：
2002-09-01
影响因子：
6.5
通讯作者：
Ikezawa, Z
中科院分区：
文献类型：
--
作者：
Iwasaki, M;Nagata, K;Ikezawa, Z
已知前列腺素D-2是由过敏原激活的肥大细胞产生的主要前列腺素类，但由于其受体系统的复杂性和缺乏合适的抑制剂，其在过敏性疾病形成中的作用尚未完全确定。我们最近发现了一种新型的前列腺素D2受体，命名为CRTH 2。对正常受试者的研究表明，CRTH 2似乎选择性地由循环CD 4（+）淋巴细胞中的辅助性T细胞2表达，而不是辅助性T细胞1。然而，在各种疾病环境中CRTH 2和辅助性T细胞2之间的确切相关性以及CRTH 2介导的前列腺素D-2活性对体内各种辅助性T细胞2应答的影响仍有待阐明。在这项研究中，我们研究了正常成人和特应性皮炎患者（一种涉及辅助性T细胞2的疾病）循环CD 4+淋巴细胞中CRTH 2和辅助性T细胞2之间的相关性。结果表明，几乎所有的CRTH 2（+）CD 4（+）淋巴细胞都具有纯的辅助性T细胞2表型，并形成正常和特应性皮炎受试者的循环辅助性T细胞2的大部分，但不是全部。在趋化性试验中，外周血CRTH 2（+）CD 4（+）淋巴细胞被前列腺素D2以及典型的T辅助细胞-2-吸引趋化因子胸腺和活化调节趋化因子显著吸引，而它们对典型的T辅助细胞-1-吸引趋化因子巨噬细胞炎性蛋白1 β和干扰素-γ诱导蛋白10几乎没有趋化性迁移。此外，在特应性皮炎患者中，在疾病相关的皮肤淋巴细胞相关抗原阳性的区域中注意到CRTH 2（+）细胞的优先增加，而不是皮肤淋巴细胞相关抗原阴性的CD 4（+）淋巴细胞区域。我们的研究结果表明，前列腺素D-2/CRTH 2系统参与正常和致病性辅助性T细胞2的反应。
Prostaglandin D-2 is known to be the major prostanoid produced by allergen-activated mast cells, but its role in the formation of allergic diseases is not well established because of complexity of its receptor system and lack of appropriate inhibitors. We have recently identified a new-type prostaglandin D2 receptor, named CRTH2. Studies with normal subjects have shown that CRTH2 appears to be selectively expressed by T helper 2 cells but not T helper 1 cells among circulating CD4(+) lymphocytes. The exact correlation between CRTH2 and T helper 2 cells in various disease settings and the impact of CRTH2-mediated prostaglandin D-2 activities on various T helper 2 responses in vivo still remain to be elucidated, however. In this study, we investigated the correlation between CRTH2 and T helper 2 cells among circulating CD4+ lymphocytes in normal adults and patients with atopic dermatitis, a T-helper-2-involving disease. The results showed that virtually all CRTH2(+)CD4(+) lymphocytes had a pure T helper 2 phenotype and formed not all but a large proportion of circulating T helper 2 cells for both normal and atopic dermatitis subjects. In chemotaxis assays, peripheral blood CRTH2(+)CD4(+) lymphocytes were significantly attracted by prostaglandin D2 as well as by a typical T-helper-2-attracting chemokine, thymus and activation regulated chemokine, whereas they showed little chemotactic migration toward typical T-helper-1-attracting chemokines, macrophage inflammatory protein 1beta and interferon-gamma inducible protein 10. Furthermore, in atopic dermatitis patients, a preferential increase of CRTH2(+) cells was noted within the disease-related cutaneous lymphocyte-associated antigen-positive, but not the cutaneous lymphocyte-associated antigen-negative, CD4(+) lymphocyte compartment. Our results suggest the involvement of the prostaglandin D-2/CRTH2 system in both normal and pathogenic T helper 2 responses.