NRP-1 as a modulator of immune cell biology

NRP-1 作为免疫细胞生物学调节剂

• 批准号: RGPIN-2018-05631
• 负责人: Delisle, JeanSebastien
• 金额: $ 4.66万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=760584
• 关键词: NRP; modulator; immune; cell; biology

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.

该项目旨在研究来自细胞外部的某些信号如何控制细胞功能。在由数十亿个细胞组成的生物体中，每个细胞都是一个单元，必须不断解释来自环境的线索并做出适当的反应。这是通过细胞表面的受体介导的，这些受体通过与细胞内部通信来监测环境并协调细胞反应。在树突状细胞（一种负责刺激免疫反应的免疫细胞）中，我们发现受体Neuropilin-1对传递干扰树突状细胞功能的信号至关重要。此外，我们的研究结果表明，Neuroplin-1通过限制与另一种受体结合后的信号来实现这一点，这种受体称为TLR 4。本项目旨在更好地了解Neuropilin-1如何干扰树突状细胞和其他免疫细胞类型中的TLR 4。更具体地说，我们将研究Neuropilin-1和TLR 4在树突状细胞中的位置和如何相互作用。我们将观察细胞表面的不同区域以及细胞内的特定区域，并观察这如何影响树突状细胞的激活。这些实验将扩展到TLR 4家族中的其他受体，以观察Neuropilin-1是否干扰树突细胞中与TLR 4相同家族的其他活化受体传递的信号。我们还将研究神经纤毛蛋白-1的其他结合伙伴（其他受体或其他细胞成分），这可能解释其在树突状细胞中的功能。最后，我们知道TLR 4信号传导在免疫系统中也表达NRP-1的许多其他细胞类型中很重要。我们将确定我们在树突状细胞中NRP-1和TLR 4之间相互作用的发现是否也适用于其他免疫细胞类型，如巨噬细胞，中性粒细胞和一些T细胞亚群。 该项目扩展了我们先前的发现，首次将Neuropilin-1和TLR 4信号联系起来。我们的目标是更好地定义这种相互作用，它可以决定树突状细胞和其他可能的免疫细胞功能。因此，该项目将进一步定义Neuropilin-1在免疫细胞功能中的作用，并为免疫细胞如何整合来自多种受体的外部信号提供新的见解。我们的研究将加强加拿大的免疫学科学，并巩固将在科学和工程领域加入劳动力队伍的几名学生的专业知识和培训。