Correlation of disease evolution with progressive inflammatory cell activation and migration in the IL-4 transgenic mouse model of atopic dermatitis.
Correlation of disease evolution with progressive inflammatory cell activation and migration in the IL-4 transgenic mouse model of atopic dermatitis.
复制标题
IL-4 转基因小鼠特应性皮炎模型中疾病演变与进行性炎症细胞激活和迁移的相关性。
DOI：
10.1111/j.1365-2249.2004.02691.x
复制
发表时间：
2005
影响因子：
4.6
通讯作者：
Chan,LS
中科院分区：
文献类型：
--
作者：
Chen,Lin;Martinez,O;Venkataramani,P;Lin,S-X;Prabhakar,BS;Chan,LS
特应性皮炎是一种慢性炎症性皮肤病，其特征在于皮肤中的炎性细胞浸润。为了评估炎症细胞在这种疾病中的作用，我们分析了活化状态和各种白细胞的表面标志物的IL-4转基因小鼠模型的特应性皮炎，流式细胞术，免疫荧光显微镜，T细胞增殖试验。这些研究是用非转基因小鼠对照和转基因小鼠在三个疾病阶段进行的：疾病发作前，早期皮肤病和晚期皮肤病，这样我们就可以描绘出免疫学事件的顺序。随着皮肤病的发展，IL-4-Tg小鼠的皮肤引流淋巴结细胞显示自发增殖和对刺激物（包括抗-CD 3、Con A、PHA和葡萄球菌肠毒素A和B）的逐渐增强的增殖反应。随着疾病的发展，淋巴器官T细胞表达活化分子的百分比（CD 44和CD 69）和共刺激分子在次级淋巴器官中，T细胞的百分比和总数以递增的方式减少，而浸润皮肤的T细胞的数量以递增的方式增加;树突状抗原呈递细胞、巨噬细胞和NK细胞的总数在淋巴器官中逐渐增加。总的来说，我们的研究结果表明，活化的炎症细胞从次级淋巴器官持续和进行性迁移到皮肤中，在那里它们参与免疫应答，导致与炎症相关的病理学。
Atopic dermatitis is a chronic inflammatory skin disease characterized by inflammatory cell infiltration in the skin. In order to assess the roles of inflammatory cells in this disease, we analysed the activation status and surface markers of various leucocytes in the IL-4 transgenic mouse model of atopic dermatitis, by flow cytometry, immuofluorescence microscopy, and T cell proliferation assays. The studies were performed with a nontransgenic mouse control and transgenic mice at three disease stages: before disease onset, early skin disease, and late skin disease, so that we can delineate the immunological sequence of events. As the skin disease evolves, the skin draining lymph node cells from IL-4-Tg mice show a spontaneous proliferation and a progressively enhanced proliferative response to stimulants including anti-CD3, Con A, PHA, and Staphylococcus enterotoxins A and B. As the disease evolves, the percent of lymphoid organ T cells expressing activation molecules (CD44 and CD69) and costimulatory molecules (ICOS and PD-1) are progressively increased; the percent and total number of T cells are reduced in an incremental manner in the secondary lymphoid organs while the number of T cells infiltrating the skin increases in an incremental fashion; the total number of dendritic antigen presenting cells, macrophages, and NK cells gradually increases in the lymphoid organs. Collectively, our results suggest that there is a continued and progressive migration of activated inflammatory cells from the secondary lymphoid organs into the skin where they participate in immune responses resulting in the pathology associated with inflammation.