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和 自身免疫性疾病的获得性免疫。UCACE有两个压倒一切的目标。第一个是确定 自身免疫性疾病中获得性自身免疫是如何演变和原位传播的 器官受累。我们将集中讨论狼疮性肾炎(LUP)，这是最常见的严重表现 系统性红斑狼疮(SLE)。进展为肾功能衰竭与肾小管间质 炎症(TII)和与TII相关的免疫过程是肾脏固有的。这些 过程不能完全反映在外周血中，SLE小鼠模型不能模拟原位 人类狼疮TII的获得性免疫反应。因此，动物模型不能替代原始模型 在人体上的研究。在ACE的最后一个周期中，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，表达这些抗体并鉴定 它们所结合的抗原。然而，识别原位识别的抗原还不足以理解 这些B细胞是如何被原位选择的。正如合作项目和试点项目中所述，我们有 开发了新的计算工具来识别同源细胞：细胞相互作用和全球模式 人类炎症中的细胞组织。在协作项目中，我们将把这些研究扩展到 其他疾病状态建立原位耐受失败的特定和全球机制 自身免疫力。 UCACE将追求的第二个目标是对第一个目标的补充。而第一个解决的是如何 自身免疫在原位传播，第二个检查耐受性丧失的后果，以及 自身免疫，在对感染产生保护性免疫的过程中。令人惊讶的是，SLE患者增加了更多 对流感疫苗接种的有效体液免疫反应优于正常对照。在初级项目中， 我们将确定增强的保护性免疫是否是更广泛的免疫球蛋白的结果 与SLE相关的曲目和/或如果SLE的细胞因子环境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.