Prediction of natural killer cell education and repertoire formation by donor immunogenetics

通过供体免疫遗传学预测自然杀伤细胞教育和库形成

• 批准号: RGPIN-2017-06489
• 负责人: Boudreau, Jeanette
• 金额: $ 1.89万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=645933
• 关键词: Prediction; natural; killer; cell; education

Natural killer (NK) cells are white blood cells that are part of the immune system, and have not been studied extensively. We do not yet understand how NK cells function because the genes and molecules that control them are very complex, and we are still establishing the tools and computational programs to study this complexity. Our NSERC program aims to understand how genes and molecules control NK cells to make them function differently between people. We are hoping to understand the extent of NK cell diversity, and how a limited number of genes can lead to such dramatic changes in the function of the immune system.******In this NSERC project, we will examine small subset of genes that are involved in NK cell function. For these genes, called KIR3DL1 and HLA-B, we already have good tools and computer programs in place. Therefore, we can use KIR3DL1 and HLA-B as a starting point to understand how NK cells are driven to have different functions. In our first aim, we will categorize NK cells based on their known features, then measure the markers that make them more or less sensitive to become activated. In the next part of our studies, we will use the same categories of NK cells, and study how the cell reacts to stimulation. We can do this by triggering the activating receptors on cell surfaces with different amounts of power, then measuring how the cell responds. ******NK cell function differs between people and changes if they are moved to a different person, or they are exposed to a new environment, which is similar to what happens during pregnancy, when a person becomes sick, or during the development of their immune system. By studying these changes, we can understand how NK cells become programmed. I recently showed that we can make NK cells change their functions in a similar way by using a new mouse model. In this NSERC project, we now plan to study the features that control NK cell function by measuring them before and after they have been changed by the new “environment” that we will create by putting them into these mice. ******NK cells are highly understudied, but they represent up to 30% of the white blood cells in the human body. We already know that they function differently from other white blood cells, and the studies that propose will help us to understand how genes control their unique function. These experiments are important because they explore a feature of the immune system that we do not understand, guiding us toward a more complete understanding of how the immune system works.

自然杀伤（NK）细胞是免疫系统的一部分，是白色血细胞，尚未被广泛研究。我们还不了解NK细胞的功能，因为控制它们的基因和分子非常复杂，我们仍在建立研究这种复杂性的工具和计算程序。我们的NSERC计划旨在了解基因和分子如何控制NK细胞，使它们在人与人之间发挥不同的功能。我们希望了解NK细胞多样性的程度，以及有限数量的基因如何导致免疫系统功能发生如此巨大的变化。在这个NSERC项目中，我们将研究参与NK细胞功能的一小部分基因。对于这些被称为KIR 3DL 1和HLA-B的基因，我们已经有了很好的工具和计算机程序。因此，我们可以使用KIR 3DL 1和HLA-B作为起点来了解NK细胞是如何被驱动以具有不同功能的。在我们的第一个目标中，我们将根据NK细胞的已知特征对其进行分类，然后测量使它们对激活或多或少敏感的标志物。在我们研究的下一部分，我们将使用相同类别的NK细胞，并研究细胞如何对刺激做出反应。我们可以通过用不同的功率触发细胞表面的激活受体来做到这一点，然后测量细胞的反应。**NK细胞的功能在人与人之间存在差异，如果它们被转移到不同的人身上，或者暴露在新的环境中，就会发生变化，这与怀孕期间发生的情况相似，当一个人生病时，或者在他们的免疫系统发育期间。通过研究这些变化，我们可以了解NK细胞是如何被编程的。我最近证明，我们可以通过使用一种新的小鼠模型，以类似的方式改变NK细胞的功能。在这个NSERC项目中，我们现在计划研究控制NK细胞功能的特征，方法是测量它们在被我们将通过将它们放入这些小鼠中而创造的新“环境”改变之前和之后的变化。******NK细胞的研究非常不足，但它们占人体白色血细胞的30%。我们已经知道它们的功能与其他白色血细胞不同，这些研究将有助于我们了解基因如何控制它们的独特功能。这些实验很重要，因为它们探索了我们不了解的免疫系统的一个特征，引导我们更全面地了解免疫系统的工作原理。