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Establishment of tretments for patients with atopic dermatitis based on the immunological background

基于免疫学背景建立特应性皮炎患者的治疗方法

基本信息

批准号：
14570795
负责人：
TERUI Tadashi
金额：
$ 1.92万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570795/
关键词：
Atopic dermatitis immuno-therapy CpG oligodeoxynucleotide eosinophilic inflammation Th2 interleukin 5

项目摘要

The number of patients with severe atopic dermatitis (AD), who show an eosinophil-related late phase skin reaction and high levels of IgE, is increasing, although there is accumulating evidence revealing its pathomechanism. Ag-nonspecific immunosuppressants have been used for the treatment of AD. These therapeutic agents sometime cause the deterioration of the host immunologic defense. AD is associated with skewing of immune response towards Th2 phenotype. There is a real need for developing an antigen-specific treatment to selectively suppress Th2 cell-mediated responses. Oligodeoxynucleotides (ODN) containing CpG motifs have been highlighted as an immunomodulator that reduces Th2-mediated responses by biasing the T-cell response toward a Th1-dominant phenotype. To substantiate the effect of CpG ODN in the Th2-mediated skin inflammation, we introduced a unique cutaneous model of a protein-Ag-induced eosinophilic inflammation with increased levels of serum IgE in BALB/c by three-time i.p. priming with ovalbumin (OVA)/alum and following a week-OVA skin patching.. Intradermal administration of CpG ODN diminished the number of infiltrated eosinophils and IgE systemic response. Interestingly, intradermal CpG ODN at the site of OVA patching significantly augmented the inhibitory effects on both the eosinophil infiltration and IgE levels and more effective when administered with Ag. Our data suggest that a cutaneous administration of CpG ODN with Ag can work as a novel Ag-specific immunomodulator therapy to treat the cutaneous eosinophilic inflammation that can be found in patients with AD.

尽管有越来越多的证据揭示了其病理机制，但患有严重特应性皮炎（AD）的患者数量正在增加，这些患者表现出嗜酸性粒细胞相关的晚期皮肤反应和高水平的 IgE。 Ag非特异性免疫抑制剂已用于治疗 AD。这些治疗剂有时会导致宿主免疫防御的恶化。 AD 与免疫反应偏向 Th2 表型有关。确实需要开发一种抗原特异性治疗方法来选择性抑制 Th2 细胞介导的反应。含有 CpG 基序的寡脱氧核苷酸 (ODN) 已被认为是一种免疫调节剂，可通过使 T 细胞反应偏向 Th1 主导表型来减少 Th2 介导的反应。为了证实 CpG ODN 在 Th2 介导的皮肤炎症中的作用，我们引入了一种独特的蛋白质 Ag 诱导的嗜酸性粒细胞炎症皮肤模型，通过 3 次腹腔注射，BALB/c 中血清 IgE 水平增加。用卵清蛋白 (OVA)/明矾启动，并在 OVA 皮肤贴敷一周后。皮内施用 CpG ODN 减少了浸润的嗜酸性粒细胞数量和 IgE 全身反应。有趣的是，OVA 修补部位的皮内 CpG ODN 显着增强了对嗜酸性粒细胞浸润和 IgE 水平的抑制作用，并且与 Ag 一起施用时更有效。我们的数据表明，CpG ODN 与 Ag 的皮肤给药可以作为一种新型 Ag 特异性免疫调节剂疗法，用于治疗 AD 患者中出现的皮肤嗜酸性粒细胞炎症。