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，同时保持对正常“自我”组织的耐受性。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。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）中却知之甚少。这些细胞检测、捕获和显示来自宿主细胞和微生物到T淋巴细胞的衍生物，并将炎症介质分泌到周围组织环境中。我们对先天免疫受体相互作用及其下游信号传导的调控感兴趣，并开发了遗传，生化和细胞方法来解决这一生物学问题。我们的NSERC项目将确定先天抑制受体信号调节蛋白α (SIRPa)调节巨噬细胞吞噬和对细胞目标的分泌反应的机制。

In vertebrates, multiple systems collaborate to ensure recognition and elimination of cells that are aged, defective or infected, while preserving tolerance to normal “self” tissues. Immune homeostasis requires a balance between activating receptors that promote responses and inhibitory receptors that maintain self-tolerance. This interplay has been studied extensively in lymphocytes that mediate adaptive immunity, but is less well understood in innate immune cells such as macrophages. These cells detect, capture and display derivatives from both host cells and microbes to T lymphocytes, and secrete inflammatory mediators into the surrounding tissue environment. We are interested in the regulation of innate immune receptor interactions and their down stream signalling, and have developed genetic, biochemical and cellular approaches to address this biology. Our NSERC program will identify the mechanisms of innate inhibitory receptor signal regulatory protein alpha (SIRPa) regulation of macrophage phagocytosis and secretory responses to cellular targets.