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Study on homing receptor expression on allergen-stimulated T cells in the pathogenesis of allergic diseases such as asthma and food allergy

过敏原刺激T细胞归巢受体表达在哮喘、食物过敏等过敏性疾病发病机制中的研究

基本信息

批准号：
11670435
负责人：
KOHNO Yoichi
金额：
$ 2.3万
依托单位：
Chiba University School of Medicine
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

项目摘要

We found that levels of expression of integrin alpha 4 on Dermatophagoides farinae (Df) antigen-stimulated peripheral blood T cells correlated with disease severity in children with Df-sensitive asthma. The results indicate the importance of homing receptor on allergen-reactive T cells in the pathophysiology of allergic diseases. In order to investigate the mechanisms of involvement of selective target organs in food allergy which is a very common allergic disease in ealry childfood, we studied expression of alpha E beta 7 integrin and cutaneous lymphocyte antigen (CLA) on T cells stimulated with cow's milk protein and hen egg white protein in food-related atopic dermatitis children. CLA was induced on peripheral T cells only in patients with food-allergic dermatitis patients in whom diagnosis was confirmed by food challenge test indicating the involvement of CLA.In contrast, no alpha E beta 7 integrin was induced in these subjects. The results indicate the distinct role of CLA in the pathophysiology in atopic dermatiitis. We thus studied the expression of CLA and alpha E beta 7 integrin on cord blood T cells upon stimulation with milk protein and subsequent development of milk-induced dermatitis. Very interstingly alpha E beta 7 integrin but not CLA was induced on cord blood T cells in some babies and this induction predict subsequent developnment of milk-induced dermatitis. Based on these findings we propose that alpha E beta 7 ibtegrin out food-reactive T cells is a key homing receptor in pathogensis of food-induced dermatitis in young infants.

我们发现粉尘螨(DF)抗原刺激的外周血T细胞上整合素α4的表达水平与DF敏感型哮喘儿童的疾病严重程度相关。这些结果表明，过敏原反应性T细胞上的归巢受体在变态反应性疾病的病理生理学中具有重要作用。为了探讨选择性靶器官在儿童食物过敏中的作用机制，我们研究了食源性特应性皮炎儿童在牛奶蛋白和蛋清蛋白刺激下T细胞表面整合素αEβ7和皮肤淋巴细胞抗原(CLA)的表达。CLA仅在食物过敏皮炎患者的外周T细胞上被诱导，在这些患者中，食物挑战试验证实了CLA的参与。相反，在这些受试者中没有诱导出αEβ7整合素。结果表明，共轭亚油酸在特应性皮炎的病理生理学中具有明显的作用。因此，我们研究了在牛奶蛋白刺激下脐血T细胞上CLA和αEβ7整合素的表达以及随后发生的奶源性皮炎。非常有趣的是，在一些婴儿的脐带血T细胞上诱导了αEβ7整合素，而不是CLA，这种诱导预测了乳源性皮炎的后续发展。基于这些发现，我们认为αEβ7整合素外食物反应性T细胞是婴幼儿食源性皮炎发病机制中的一个关键归巢受体。