Innate Recognition of Allogeneic Non-Self

摘要 先天免疫系统负责早期的非自我识别事件， 适应性免疫虽然先天免疫系统识别 微生物的非自我已经得到很好的定义，目前还不知道先天免疫系统是如何 感觉同种异体的非我。我们已经发现单核细胞对 T、B和NK细胞非自身独立的同种异体。这种反应导致持续的 移植后单核细胞分化为成熟的树突状细胞（DC）， 用于间接同种异体抗原呈递。在这份拨款申请中，我们建议界定（1） 急性和慢性排斥反应中单核细胞的先天同种异体识别，以及（2） 单核细胞感知同种异体的非自身。为了实现这些目标，我们将利用 转基因和基因敲除小鼠，其中特定的细胞类型和分子途径可以 跟踪或删除。遗传工具，以确定机制的先天同种异体识别也将 就业。拟议的研究是创新和重要的，因为它们代表了一种转变 在我们对移植器官的先天免疫反应的思考中， 以特异性和安全的方式中断先天免疫激活的靶点。

Abstract The innate immune system is responsible for the early non-self recognition events that lead to adaptive immunity. Although the mechanisms by which the innate immune system recognizes microbial non-self have been well defined, it is not known how the innate immune system senses allogeneic non-self. We have discovered that monocytes mount a specific response to allogeneic non-self independent of T, B, and NK cels. This response leads to persistent monocyte differentiation to mature dendritic cells (DC) after transplantation and is responsible for indirect alloantigen presentation. In this grant application we propose to define (1) the role of innate allorecognition by monocytes in acute and chronic rejection, and (2) the mechanisms by which monocytes sense allogeneic non-self. To accomplish these aims we will utilize transgenic and gene-knockout mice in which specific cell types and molecular pathways can be tracked or deleted. Genetic tools to identify mechanisms of innate allorecognition will also be employed. The proposed studies are innovative and significant because they represent a shift in our thinking about the innate immune response to transplanted organs and could yield novel targets for interrupting innate immune activation in a specific and safe manner.