NRP-1 as a modulator of immune cell biology

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This project is to study how certain signals from the outside of the cell control cellular function. In living organisms, made of billions of cells, each cell is a unit that must constantly interpret cues from its environment and react appropriately. This is mediated through receptors at the surface of the cells that survey the environment and orchestrate the cellular response by communicating with the interior of the cell. In dendritic cells, an immune cell responsible to stimulate the immune response, we found that the receptor Neuropilin-1 was essential to relay a signal that interferes with dendritic cell function. Moreover, our results suggest that Neuroplin-1 does that by limiting the signals from another receptor after binding to it, a receptor called TLR4. This project aims to better understand how Neuropilin-1 interferes with TLR4 in dendritic cells and other immune cell types.******More specifically, we will investigate where and how Neuropilin-1 and TLR4 interact in dendritic cells. We will look at different areas of the cell surface as well as specific compartments inside the cell and see how this influences activation of dendritic cells. These experiments will be extended to other receptors in the TLR4 family to see if Neuropilin-1 interferes with the signals transmitted by other activation receptors of the same family as TLR4 in dendritic cells. We will also investigate what are the other binding partners of Neuropilin-1 (other receptor(s) or other cellular components) that may explain its function in dendritic cells. Finally, we know that TLR4 signaling is important in many other cell types in the immune system that also express NRP-1. We will define whether our discovery of an interaction between NRP-1 and TLR4 in dendritic cells also apply to other immune cell types such as macrophages, neutrophils and some T-cell subsets. ******This project extends our previous findings that associated Neuropilin-1 and TLR4 signaling for the first time. Our objectives are to better define this interaction which can determine dendritic, and likely other immune cell function. As such, this project will further define the roles of Neuropilin-1 in immune cell function and offer novel insights into how immune cell integrate external signals from multiple receptors. Our research will strengthen Canadian science in immunology and consolidate the expertise and training of several students who will join the workforce in areas of science and engineering.