APOPTOSIS OF ANTIGEN PRESENTING CELLS--AUTOIMMUNITY ROLE

我对自身免疫和自身免疫的发病机制产生了兴趣。 系统性风湿病通过我的临床训练和 我在免疫学研究方面获得的经验。我的切身利益 是在细胞凋亡和免疫调节方面。拟议的项目将增强 我的研究技能和将应用最先进的技术和 了解细胞凋亡和T细胞抗原作用的途径 系统性自身免疫中的递呈细胞(APC)相互作用。这 经验将使我能够实现我成为一名 独立调查员。Elkon博士的实验室在 这个项目所需的大多数技术，并取得了显著的进展 在细胞凋亡和小鼠狼疮模型领域做出了贡献。这个 专科医院的科学环境与发展 康奈尔大学医学中心提供直接访问优秀的 多机构免疫学计划，并允许密切合作 调查人员精通多个相关领域。这 环境提供了实现我目标的最佳环境。 目前建议的总体目标是研究功能 APC细胞凋亡在正常免疫调节和全身性疾病中的意义 以及定义哪些参数(细胞因子， 激活和黏附分子)是Fas介导的 APC的细胞凋亡。本提案的目标1将探讨 细胞因子与巨噬细胞表面活化和黏附 Fas中的分子介导的细胞凋亡。研究黄曲霉的选择效应 体内巨噬细胞FasR缺乏(AIM 2)、RAG/MRL/Pr和RAG/MRL/++ 小鼠将被注射MRL/++淋巴细胞，去除巨噬细胞和 比较自身免疫性疾病的发病情况和严重程度。在《目标3》中，我们将 检测Fas在树突状细胞中的功能。在目标4中，我们将扩展 正常人和病人单核细胞和巨噬细胞的研究 系统性红斑狼疮。 我们的研究将进一步探索其机制和功能。 T细胞与APC之间一种新的免疫调节途径的意义 并将扩大我们对巨噬细胞和树突状细胞的作用的认识 免疫和自身免疫中的细胞。

I have developed my interest in autoimmunity and the pathogenesis of systemic rheumatiC disease both through my clinical training and the experience I have gained in immunology research. My immediate interest is in apoptosis and immune regulation. The proposed project will enhance my research skills and will apply state of the art techniques and approaches toward understanding the role of apoptosis and T cell:antigen presenting cell (APC) interactions in systemic autoimmunity. This experience will enable me to attain my long-term goal of becoming an independent investigator. Dr. Elkon's laboratory has expertise in the majority of techniques needed for this project and has made significant contribution's in the fields of apoptosis and murine lupus models. The scientific environment of the Hospital for Special Surgery and the Cornell University Medical Center provides direct access to an excellent multi-institutional immunology program and allows close collaborations with investigators expert in a multitude of related fields. This environment provides the optimal situation in which to achieve my goals. The overall goal of the current proposal is to study the functional significance of APC apoptosis in normal immunoregulation and in systemic lupus erythematosus as well as to define which parameters (cytokines, activation and adhesion molecules) are required for Fas-mediated apoptosis of APCs. Aim 1 of this proposal will explore the roles of cytokines as well as macrophage cell surface activation and adhesion molecules in Fas mediated apoptosis. To study the selective effect of macrophage FasR deficiency in vivo (Aim 2), RAG/MRL/pr and RAG/MRL/++ mice will be injected with MRL/++ lymphocytes depleted of macrophages and the onset and severity of autoimmunity compared. In Aim 3, we will examine the function of Fas in dendritic cells. In Aim 4 we will extend our study to human monocytes and macrophages from normals and patients with SLE. Our studies will explore further the mechanism and functional significance of a novel immunoregulatory pathway between T cells and APCs and will expand our knowledge on the role of macrophages and dendritic cells in immunity and autoimmunity.