The Slamf3, Slamf5, and Slamf6 receptor-induced pathways to murine lupus

项目总结(见说明)： SLAMF受体及其接头SAP和EAT-2在人类和小鼠的先天免疫和获得性免疫反应中发挥重要作用。该项目的研究人员发现，在小鼠体内，这些受体中的几个对自身免疫的发展进行积极或消极的调节，包括狼疮相关的病理。令人兴奋的是，初步研究表明，从系统性红斑狼疮(SLE)患者分离的免疫细胞中，几种SLAMF受体启动的信号通路存在偏差。 项目1的总体假设是，小鼠受体Slamf3、5和6及其亚型控制着参与小鼠狼疮发病机制的免疫反应。为检验这一假设而设计的实验分为以下几组： 具体目标#1：验证三种Slamf6受体亚型启动狼疮不同正负调节通路的假设。 具体目的#2：验证Slamf5受体在小鼠狼疮发病过程中控制T、B细胞和DC信号的假设。 具体目标#3：验证Slamf3受体启动信号控制自身抗体产生的假设。

PROJECT SUMMARY (See instructions): SLAMF receptors and their adapters SAP and EAT-2 play a major role in human and mouse innate and adaptive immune response. Investigators in this Program Project have discovered that in mice several of these receptors either positively or negatively regulate the development of autoimmunity, including lupus related pathology. Excitingly, preliminary studies have revealed deviations in signaling pathways initiated by several SLAMF receptors in immunocytes isolated from patients with systemic lupus erythematosus (SLE). The overall hypothesis of Project #1 is that the mouse receptors Slamf3, 5, and 6 and their isoforms govern immune responses involved in the pathogenesis of murine lupus. The experiments that are designed to test this hypothesis are grouped as follows: Specific Aim#1: Testing the hypothesis that the three Slamf6 receptor isoforms initiate distinct positive and negative regulatory pathways to lupus. Specific Aim #2: Testing the hypothesis that the Slamf5 receptor governs signaling in T and B cells and DC during the pathogenesis of mouse lupus. Specific Aim #3: Testing the hypothesis that Slamf3 receptor initiated signaling controls autoantibody production.