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Study on the role of dendritic cells in the atopic dermatitis

树突状细胞在特应性皮炎中作用的研究

基本信息

批准号：
11670829
负责人：
ASADA Hideo
金额：
$ 2.3万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670829/
关键词：
atopic dermatitis T cell dendritic cell cytokine apoptosis superantigen staphylococus aureus neutralizing antibody Th1細胞 Th2細胞

项目摘要

It is known that atopic dermatitis (AD) is a Th2 dominant inflammatory skin disease, however, the mechanism of such Th1/Th2 unbalance is unknown. We hypothesized that dendritic cells, professional antigen presenting cells, have an important role to determine Th1/Th2 balance in this disease. We planed to study the role of dendritic cells on Th1/Th2 unbalance in AD.At first, to investigate the immunological status of T cells in AD patients, we assessed the proliferative response of peripheral blood mononuclear cells to staphylococcal enterotoxin B (SEB), one of the superantigens from S.aureus, which have a role in aggravation of AD.Our studies demonstrated that T cells from the patients with severe AD were prone to undergo apoptosis following SEB stimulation, and that not only Th1 but also Th2 activity was suppressed. Dendritic cells were suggested to induce T cell apoptosis. In contrast to this in vitro phenomenon, we observed few apoptotic T cells at the AD lesion with staphylococcal infection. To clarify this discrepancy, we hypothesized that anti-apoptotic activity was present in the serum of the patient. We examined whether or not sera of AD patients had any influence on T-cell response to SEB.We found that sera from severe AD patients had high titers of anti-SEB neutralizing antibody and markedly suppressed T cell proliferative response to SEB.Our findings suggest that anti-SEB neutralizing antibody may rescue T cells from apoptosis and paradoxically down-regulate inflammatory responses induced by SEB in the patients.

众所周知，特应性皮炎（AD）是一种Th2显性的炎症性皮肤病，然而，这种Th1/Th2失衡的机制尚不清楚。我们假设树突状细胞，专业抗原呈递细胞，在这种疾病中具有决定Th1/Th2平衡的重要作用。我们计划研究树突状细胞在AD患者Th1/Th2失衡中的作用。首先，为了研究AD患者T细胞的免疫状态，我们评估了外周血单个核细胞对金黄色葡萄球菌超抗原之一的葡萄球菌肠毒素B （SEB）的增殖反应，SEB在AD的加重中起作用。我们的研究表明，重度AD患者的T细胞在SEB刺激后容易发生凋亡，不仅Th1活性受到抑制，而且Th2活性也受到抑制。树突状细胞可诱导T细胞凋亡。与这种体外现象相反，我们在葡萄球菌感染的AD病变处观察到很少凋亡的T细胞。为了澄清这种差异，我们假设患者的血清中存在抗凋亡活性。我们检查了AD患者的血清是否对SEB的t细胞反应有任何影响。我们发现严重AD患者的血清中含有高滴度的SEB抗体，并显著抑制T细胞对SEB的增殖反应。我们的研究结果表明，抗SEB中和抗体可能拯救T细胞免于凋亡，并矛盾地下调SEB诱导的炎症反应。