University of Chicago Autoimmunity Center of Excellence

芝加哥大学自身免疫卓越中心（UCACE）的中心主题是耐受性， 自身免疫性疾病的适应性免疫UCACE有两个首要目标。首先是确定 适应性自身免疫是如何进化的，并在具有特定末端的自身免疫性疾病中原位传播 器官参与。我们将重点介绍狼疮性肾炎（LuN），这是最常见的严重表现， 系统性红斑狼疮（SLE）。进展为肾衰竭与肾小管间质性 因此，本发明人认识到，与TII相关的免疫过程是肾脏固有的。这些 这些过程在外周血中没有完全反映出来，SLE的小鼠模型也没有模拟原位过程。 人类TII型狼疮的适应性免疫反应。因此，动物模型不能替代原发性 人类的研究。在ACE的最后一个周期，我们开发了新的方法来研究原位免疫 在人体组织中。我们现在可以克隆原位表达的抗体，表达这些抗体并表征 它们结合的抗原然而，识别原位识别的抗原不足以理解 这些B细胞是如何被原位选择的。如合作和试点项目所述，我们 开发了新的计算工具，以确定同源细胞：细胞相互作用和全球模式， 人类炎症中的细胞组织。在合作项目中，我们将把这些研究扩展到 其他疾病状态，以建立具体的和全球性的机制，其中原位耐受失败， 自身免疫 UCACE追求的第二个目标是对第一个目标的补充。而第一个地址如何 自身免疫在原位传播，第二个检查耐受性丧失的后果， 自身免疫，在保护性免疫的发展感染。令人惊讶的是，SLE患者 有效的体液免疫应答流感疫苗接种比正常对照。在主要项目中， 我们将确定保护性免疫力增强是否是更广泛的免疫球蛋白的结果 与SLE相关的细胞因子库和/或SLE的细胞因子环境是否能够实现更好的保护性免疫。

The central theme of the University of Chicago Autoimmune Center of Excellence (UCACE) is tolerance and adaptive immunity in autoimmune diseases. The UCACE has two over-riding goals. The first is to determine how adaptive autoimmunity evolves and is propagated in situ in autoimmune diseases with specific end organ involvement. We will focus on lupus nephritis (LuN) which is the most common severe manifestation of systemic lupus erythematosus (SLE). Progression to renal failure correlates with tubulointerstitial inflammation (TII) and that the immunological processes associated with TII are intrinsic to the kidney. These processes are not fully reflected in the peripheral blood and murine models of SLE do not mimic the in situ adaptive immune responses of human lupus TII. Therefore, animal models cannot substitute for primary studies in humans. During the last cycle of the ACE, we developed novel methods to study in situ immunity in human tissue. We can now clone in situ expressed antibodies, express these antibodies and characterize the antigens they bind. However, identifying the antigens recognized in situ is not sufficient to understand how those B cells are being selected in situ. As described in the Collaborative and Pilot Projects, we have developed novel computational tools to identify both cognate cell:cell interactions and global patterns of cellular organization in human inflammation. In the Collaborative Project, we will extend these studies to other disease states to establish specific and global mechanisms by which in situ tolerance fails in autoimmunity. The second goal to be pursued by the UCACE is complementary to the first. While the first addresses how autoimmunity is propagated in situ, the second examines the consequences of a loss of tolerance, and autoimmunity, in the development of protective immunity to infection. Surprisingly, SLE patients mount more effective humoral immune responses to influenza vaccination than normal controls. In the Primary Project, we will determine if enhanced protective immunity is a consequence of the broader immunoglobulin repertoire associated with SLE and/or if the cytokine milieu of SLE enables better protective immunity.