Innate immune cell interactions mediated by the SIRP receptor family

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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.