Innate immune cell interactions mediated by the SIRP receptor family

在脊椎动物中，多个系统协作以确保识别和消除老化、缺陷或感染的细胞，同时保留正常的“自我”组织。免疫稳态需要激活受体促进反应和抑制受体维持自我耐受性之间的平衡。我的项目的长期目标是了解这些激活和抑制反应是如何整合的，以保持准确的自我/非自我识别。这种相互作用已经在介导适应性免疫的淋巴细胞中得到了广泛的研究，但在先天免疫细胞如巨噬细胞（M?）中却知之甚少。我们已经证明，先天免疫受体信号调节蛋白-α (SIRPα)是一种抑制性受体，可以识别几乎所有健康细胞上表达的蛋白质。我建议确定SIRPα抑制M？对正常自我的反应，并被调节以允许对非自我细胞作出适当的反应。

In vertebrates, multiple systems collaborate to ensure recognition and elimination of cells that are aged, defective or infected, while preserving normal “self” tissues. Immune homeostasis requires a balance between activating receptors that promote responses and inhibitory receptors that maintain self-tolerance. The long-term goal of my program is to understand how these activating and inhibitory responses are integrated to maintain accurate self/non-self recognition. This interplay has been studied extensively in lymphocytes that mediate adaptive immunity, but is less well understood in innate immune cells such as macrophages (M?). We have shown that the innate immune receptor Signal Regulatory Protein-α (SIRPα) is an inhibitory receptor that recognizes a protein expressed on virtually all healthy cells. I propose to identify the signalling pathways and down-stream mediators by which SIRPα inhibits M? responses to normal self and is regulated to allow appropriate responses to non-self cells.