IFNλ1对系统性红斑狼疮树突细胞分化成熟及功能的作用研究

项目名称： IFNλ1对系统性红斑狼疮树突细胞分化成熟及功能的作用研究

项目编号： No.81501399

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 吴倩

作者单位： 山东大学

项目金额： 18万元

中文摘要： 系统性红斑狼疮(SLE) 是一种多发于育龄期女性，累及肾脏、皮肤、心脏等多脏器的自身免疫性疾病。树突细胞(dendritic cell, DC) 作为一种专职抗原递呈细胞，其功能活化与SLE发病密切相关。.我们的前期研究发现干扰素λ1(IFNλ1) 在SLE外周血中显著上调，与疾病进展密切相关，并能在体外诱导单核细胞分化为DC表型。因此我们假设：IFNλ1通过诱导单核细胞分化为树突细胞，进而诱导致病性CD4+T细胞活化，刺激B细胞分泌自身抗体，导致SLE发病或疾病进展。为验证该假说，我们将采用免疫磁珠分选SLE患者外周血单核细胞，检测IFNλ1诱导单核细胞分化为致病性DCs的作用，并在狼疮小鼠模型中验证IFNλ1的致病作用，探讨IFNλ1在SLE发病中的重要作用和机制。本研究将从IFNλ1这个新视点为揭示SLE的发病机制奠定理论基础，为SLE临床防治提供新的研究思路。

中文关键词： 红斑狼疮；系统性；风湿免疫性疾病；自身免疫性；自身免疫调节因子；干扰素λ1

英文摘要： Systemic lupus erythematosus(SLE) is an autoimmune disease that predominantly affects women abd typically has manifestations in multiple organs such as kidney, skin and heart. Dendritic cell as a kind of professional antigen-presenting cell, was identifeid to play a critical role in the development of SLE..We reported that inteferon lambda 1(IFNλ1) is significantly upregulated in the serum of SLE patients and associated with the SLE development.Meanwhile, our preliminary results indicate that IFNλ1 induced the generation of DCs derived from monocytes in vitro. Therefore, we hypothesize IFNλ1 increases the activities of CD4+T cells and B cells by inducing the generation of DCs derived from monocytes, resulting the pathogenesis and development of SLE. To test the hypothesis, we will explore the functions and mechanism of IFNλ1 in SLE by using various techniques including immunomagnetic beads,ELISA and flow cytometry in SLE patients and animal models. This study will provide a sound theoretical basis and a novel way for the research and therapy of SLE.

英文关键词： lupus erythematosus; systemic;rheumatic disease;autoimmunity ;autoimmune regulator ;interferon λ1