UAB Autoimmunity Center for Excellence

描述（由申请人提供）：伯明翰的亚拉巴马大学（UAB）在基础免疫学和自身免疫性疾病的新型转化疗法的测试方面有着出色的记录。UAB自身免疫卓越中心（ACE）是一个多学科的合作计划，旨在联合这些优势，加速自身免疫性疾病转化疗法的开发和测试。为了实现这一目标，UAB ACE将促进基础和转化研究，并赞助新型免疫调节剂的临床试验。作为这一使命的一部分，UAB ACE将促进基础和临床研究人员之间的沟通，以及UAB和全国范围内专注于不同免疫介导疾病的研究人员之间的沟通。 提出了四个项目。 临床部分（项目1）包括来自六个临床领域的经验丰富的研究人员。提出了两项潜在的临床试验，靶向狼疮中的死亡受体5，这是UAB开发的一种方法，以及银屑病关节炎中的IL-1，使用制药行业带给UAB研究人员的高亲和力阻滞剂。三个基本项目集中在分析T细胞和细胞因子和/或TNF家族因子在维持或恢复耐受性中的相互作用的统一主题上，包括：项目2）死亡受体5在自身免疫中活化T细胞上的功能，项目3）细胞因子和TNF家族蛋白在免疫抑制后T细胞耐受重建中的作用，和项目4）表达IL 10的T细胞在粘膜免疫耐受中的功能。这些项目的互动性质说明了这样一个事实，即每个基本项目都涉及来自至少一个其他项目的分析或模型。行政核心将协调ACE活动，促进互动和合作，促进科学发展，制定战略议程，并对正在进行的项目进行持续评估。免疫调节研究核心将促进对疾病中人体组织中细胞或细胞因子变化的分析，以及对接受生物治疗的参与者的机制研究。 这两个核心将服务于所有拟议项目。 因此，ACE将联合UAB研究人员，将免疫学研究的力量和一系列免疫介导疾病的临床试验经验的气息结合起来，共同开发新的自身免疫疗法。

DESCRIPTION (provided by applicant): The University of Alabama at Birmingham (UAB) has an outstanding record in basic immunology and in testing of novel, translational therapies for autoimmune diseases. The UAB Autoimmunity Center of Excellence (ACE) is a multidisciplinary, collaborative program to unite these strengths to accelerate the development and testing of translational therapies for autoimmune disease. To accomplish this, the UAB ACE will promote basic and translational research and sponsor clinical trials of novel immunomodulatory agents. As part of this mission, the UAB ACE will foster communication between basic and clinical investigators and between those focused on different immune-mediated diseases at UAB and nationally. Four projects are proposed. The Clinical Component (Project 1) includes highly experienced investigators from six clinical areas. Two potential clinical trials are proposed, targeting Death Receptor 5 in Lupus, an approach developed at UAB, and IL-1 in psoriatic arthritis, using a high affinity blocker brought to UAB investigators by the pharmaceutical industry. Three basic projects center on the unifying theme of analysis of the interaction of T cells and cytokines and/or TNF-family factors in maintenance or restoration of tolerance, including: Project 2) function of Death Receptor 5 on activated T cells in autoimmunity, Project 3) the role of cytokines and TNF-family proteins in reconstitution of T cell tolerance after immunosuppression, and Project 4) the function of IL10-expressing T cells in tolerance in mucosal immunity. The interactive nature of these projects is illustrated by the fact that each basic project involves assays or models derived from at least one of the others. The Administrative Core will coordinate ACE activities, facilitate interactions and collaborations, promote scientific development, set the strategic agenda, and perform continuous evaluation of ongoing projects. The Immunomodulatory Studies Core will promote analysis of changes in cells or cytokines in human tissues in disease and in mechanistic studies of participants receiving biologic therapies. Both cores will serve all proposed projects. Thus, the ACE will unite UAB investigators to bring the strength of immunological research and the breath of experience in clinical trials in a range of immune-mediated diseases to jointly develop new therapies for autoimmunity.