Project-002

Emory自身免疫卓越中心（ACE）U19的总体目标是 破译负责异常效应免疫应答的分子程序， 导致自身免疫性疾病。具体来说，根据埃默里ACE所做的工作， 在目前的资助周期中，我们假设效应B细胞的表观遗传调控 分化和功能是系统性狼疮的关键致病成分 红斑狼疮（SLE）。此外，我们认为，疾病相关的表观遗传印记是第一个 在B细胞发育的早期阶段建立，然后在整个 通过抗原和共刺激活化，幼稚细胞分化成其效应子后代。 刺激途径。最后，我们提出SLE也将以异常 调节其他关键的效应免疫应答，即CD 8 T细胞，特别是， 干细胞样群体负责维持抗原特异性应答， 慢性病毒感染和检查点抑制剂治疗患者的抗肿瘤反应。 Emory ACE的基本目标是：1）了解B细胞和CD 8 T细胞 在人类SLE中的失调;和2）组装一个科学和技术平台， 与其他ACE U19和UM 1中心合作，在其他免疫细胞中进行类似研究 和自身免疫性疾病。Emory ACE U19的具体目标是：目标1：建立 行政核心（一）Sanz，核心总监）成功运营ACE U19 科学方案及其与ACE网络的互动;目标2： 综合埃默里大学ACE U19科学计划包括以下组成部分： 主要项目（Sanz，PI）：人类SLE中B细胞失调的机制;合作 项目（Boss，PI）：自身免疫反应的表观遗传调节;试点项目（Ahmed，PI）： SLE中干细胞样CD 8 T细胞的特征预期的结果将揭开疾病 发病机制;细分患者;设计个性化治疗;并开发生物标志物 疾病的发生、演变和结果。我们的努力自然将与联合国的使命相吻合。 UM 1 ACE以ACE网络的宪章使命为中心，并为之做出了巨大贡献。

The overarching objective of the Emory Autoimmunity Center of Excellence (ACE) U19 is to decipher the molecular programs responsible for the aberrant effector immune responses that lead to autoimmune disease. Specifically, based on the work performed by the Emory ACE during the current funding cycle, we postulate that epigenetic regulation of effector B cell differentiation and function is a critical pathogenic component of Systemic Lupus Erythematosus (SLE). Further, we contend that disease-related epigenetic imprinting is first established at early stages of B cell development and then maintained throughout the differentiation of naïve cells into their effector progeny upon activation by antigens and co- stimulatory pathways. Finally, we propose that SLE will also be characterized by abnormal regulation of other critical effector immune responses, namely CD8 T cells and in particular, the stem-like population responsible for the maintenance of antigen-specific responses in chronic viral infections and anti-tumor responses in patients treated with checkpoint inhibitors. The fundamental goals of the Emory ACE are: 1) to understand B cells and CD8 T cells dysregulation in human SLE; and 2) to assemble a scientific and technological platform that engages other ACE U19 and UM1 Centers to perform similar studies in other immune cells and autoimmune disorders. The specific aims of the Emory ACE U19 are: Aim 1: To establish an Administrative Core (I. Sanz, Core Director) for the successful operation of the ACE U19 Scientific Program and its interaction with the ACE Network; Aim 2: To develop a highly integrated Emory ACE U19 Scientific Program comprised of the following components: Principal Project (Sanz, PI): Mechanisms of B cell dysregulation in human SLE; Collaborative Project (Boss, PI): Epigenetic regulation of autoimmune responses; Pilot Project (Ahmed, PI): Characterization of stem-like CD8 T cells in SLE. The expected results will unravel disease pathogenesis; segment patients; design personalized therapies; and develop biomarkers of disease onset, evolution, and outcome. Our efforts will naturally dovetail with the mission of the UM1 ACEs centers and contribute greatly to the charter mission of the ACE network.