Th22细胞干扰角质形成细胞分泌HB-EGF与其在银屑病发病中的作用探讨

项目名称： Th22细胞干扰角质形成细胞分泌HB-EGF与其在银屑病发病中的作用探讨

项目编号： No.81201231

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 罗素菊

作者单位： 天津医科大学

项目金额： 23万元

中文摘要： 银屑病是最常见的皮肤病之一，病因不清，难以治愈。目前认为银屑病的发病机制主要为由T细胞介导的以角质形成细胞（KC）为靶点的免疫应答反应。Th22细胞是新认识的一种T细胞亚群，参与银屑病的发生。课题组前期研究证明肝素结合表皮生长因子样生长因子（HB-EGF）在银屑病表皮KC异常增殖中发挥重要作用。我们推测Th22细胞可能通过干扰KC中HB-EGF的表达，进而影响银屑病的发生。本研究运用分子生物学，免疫学和细胞生物学等先进技术，以临床标本，Th22细胞及其细胞因子干预后培养的KC、皮肤类似物模型和银屑病动物模型为研究对象，检测银屑病患者皮损及外周血Th22细胞及其效应细胞因子的表达情况，检测干预前后KC增殖和凋亡的改变、观察皮肤类似物模型和银屑病动物模型表皮形态的改变，检测HB-EGF表达的改变，意欲阐明Th22细胞在银屑病表皮KC异常增殖中的作用，为揭示银屑病的发病机制奠定基础。

中文关键词： 银屑病；角质形成细胞；HB-EGF；信号通路；TIG3

英文摘要： Psoriasis is a common skin disease with unclear etiology that involves dysregulated interplay between immune cells and keratinocytes. Th22 cell was recently identified as another new subset of T cells generated in presence of TNF-α and IL-6, which produced IL-22. Th22 cells may participate in the pathogenesis of psoriasis. Heparin-binding epidermal-growth-factor-like growth factor (HB-EGF) plays an important role in keratinocyte hyperproliferation in psoriasis as identified in our previous studies. In this study, we will collect the lesions and peripheral blood of psoriatic patients, culture keratinocytes, culture skin model and mouse model as our targeted experimental materials. Cultured keratinocytes, cultured skin model and mouse model will be treated by supernatant obtained from culturing Th22 cells, IL-22 and anti-IL-22 Ab. We will use flow cytometry to detect Th22 cells in the peripheral blood of psoriatic patients, use in situ hybridization and real time quantitative RT-PCR to detect IL-22 and HB-EGF mRNA, use immunohistochemistry and Western-blot to detect IL-22 and HB-EGF protein. We will also observe the epidermal changes of cultured skin model and mouse model after treatment. We will analyze the relation of the number of Th22 cells with psoriatic severity, of expression level of IL-22 and HB-EGF with

英文关键词： Psoriasis；keratinocyte；HB-EGF；cell signaling；TIG3