Treg在特应性皮炎样GVHD发病中的优势漂移及分子机制

项目名称： Treg在特应性皮炎样GVHD发病中的优势漂移及分子机制

项目编号： No.81472879

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张建中

作者单位： 北京大学

项目金额： 80万元

中文摘要： 我们于2013年在国际上首先报告了一种新的移植物抗宿主病- - 特应性皮炎样GVHD（AD样GVHD）,临床特征包括泛发性皮炎、剧烈瘙痒、伴发内脏排异等，由于是新发现的GVHD类型，因此发病机制的研究还为空白。调节性T细胞（Treg）具有维持免疫自稳和抑制免疫应答的特性，我们在前期研究中发现AD样GVHD患者常有血循环中Treg数量增加，皮损中有Treg细胞浸润，提示在AD样GVHD中Treg发生了优势漂移。本课题拟采用细胞共培养体系，通过分离和培养患者的Treg及相关细胞，构建AD样GVHD体外细胞模型，应用细胞与分子生物学等技术，研究不同条件下Treg的表型、细胞因子分泌模式、抗体表达、信号通路、与其他细胞间的相互作用，及其对患者皮肤屏障功能（角层超微结构、丝聚蛋白表达和经皮水丢失）等的影响，阐明Treg在AD样GVHD发病中的作用机制，为AD样GVHD的预防、早期识别和治疗提供新的思路。

中文关键词： 特应性皮炎；移植物抗宿主病；调节性T细胞；优势漂移；分子机制

英文摘要： In early 2013, we reported atopic dermatitis-like graft-versus-host disease (AD-like GVHD) for the first time in the world. It's a novel form of cutaneous GVHD and was characterized by generalized dermatitis, intense pruritus and association with internal organ's rejection. Since it's a new disease, the mechanism has not been studied yet. Regulatory T cells (Tregs) have the properties of maintaining immune homeostasis and suppressing immune response.In our pilot study, we found increased Tregs in the peripheral blood of AD-like GVHD patients and in infiltrates of skin lesions, suggesting that the dominant drift of Tregs be involved in the pathogenesis of the disease. In this study, we aimed to investigate the role of Tregs in AD-like GVHD through a co-cultured system of Tregs and other related cells in vitro, to investigate the phenotypes, cytokines profile, antibody expression and signaling pathway of Tregs by means of cellular biology and molecular biology, and to investigate the effect of Tregs on the patients' skin barrier function (ultrastructure of stratum cornium, filaggrin expression and transepidermal water loss). Furthermore, the interactions between Tregs and other cells will also be studied. This study will help to clarify the possible mechanism of Tregs in the pathogenesis of AD-like GVHD and might help in developing measures for prevention, early recognition and treatment of this novel disease.

英文关键词： atopic dermatitis;graft-versus-host disease;regulatory T cell;predominant drift;molecular mechanism