Peripheral Mechanisms of Immunologic Tolerance

描述（由申请人提供）：诱导移植和自身免疫耐受仍然是一个难以捉摸的临床目标。因此，更深入地了解免疫耐受的基本机制是必要的。我们在这里提出了一个多学科的方法来研究免疫耐受的外周机制，通过研究小鼠实体器官移植，骨髓移植和自身免疫模型。提出了一个多学科的方法，因为负责耐受性自身和外来抗原重叠的机制，因为三个临床学科之间存在显着的串扰：骨髓移植越来越多地用于诱导实体器官同种异体移植的耐受性，移植中使用的治疗药物适用于自身免疫患者（反之亦然）。 PPG由三个综合项目和一个核心项目组成：组织病理学。这些项目之间的整合是基于免疫学概念的共同性，研究人员之间正在进行和未来的合作，以及方法和资源的共享。项目1将探讨骨髓移植后树突状细胞成熟导致移植物抗宿主病（GVHD）的机制。项目2将通过在炎症性肠病小鼠模型中产生调节性T细胞（Treg）来研究耐受诱导。项目3将通过研究宿主免疫系统持续识别移植器官的先天和适应性机制来探索免疫无知现象。 组织学核心（核心B）将为所有三个项目提供组织处理、染色、免疫组织化学、原位杂交、成像和解释服务。行政核心（核心A）将提供后勤、通信和数据共享支持。

DESCRIPTION (provided by applicant): The induction of tolerance in transplantation and autoimmunity remains an elusive clinical goal. A more thorough understanding of the fundamental mechanisms of immunologic tolerance is therefore necessary. We propose here a multidisciplinary approach to investigate peripheral mechanisms of immunologic tolerance by studying murine models of solid organ transplantation, bone marrow transplantation, and autoimmunity. A multidisciplinary approach is proposed because the mechanisms responsible for tolerance to self and foreign antigens overlap, and because significant cross-talk among the three clinical disciplines exists: bone marrow transplantation is increasingly employed to induce tolerance to solid organ allografts, and therapeutic agents used in transplantation are applicable to patients with autoimmunity (and vice versa). The PPG consists of three integrated projects and a core: histopathology. Integration among the projects is based on commonality of immunologic concepts, ongoing and future collaborations between the investigators, and the sharing of methods and resources. Project 1 will explore the mechanisms of dendritic cell maturation that lead to graft-versus-host disease (GVHD) following bone marrow transplantation. Project 2 will investigate tolerance induction via the generation of regulatory T cells (Treg) in a mouse model of inflammatory bowel disease. Project 3 will explore the phenomenon of immunologic ignorance by studying the innate and adaptive mechanisms that are responsible for continued recognition of a transplanted organ by the host's immune system. The Histopathology Core (Core B) will provide tissue processing, staining, immunohistochemistry, in situ hybridization, imaging, and interpretation services to all three projects. The Administrative Core (Core A) will provide logistical, communications and data sharing support.