Exercise-dependent modulation of natural killer cells during human growth

人体生长过程中自然杀伤细胞的运动依赖性调节

• 批准号: RGPIN-2018-06774
• 负责人: Obeid, Joyce
• 金额: $ 1.75万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=714437
• 关键词: Exercise; dependent; modulation; natural; killer

Natural killer (NK) cells are a dynamic subset of lymphocytes that drive the innate and adaptive immune response. NK cells are the most responsive immune cell to acute exercise, a form of physiological stress. Children and older adults demonstrate a dampened NK cell response to specific episodes of exercise compared with young adults. Unfortunately, these data are based on cross-sectional studies and seldom concurrently examine NK cell function. Studying acute changes in NK cells is important because downregulation of NK cell number and/or function can have summative negative effects on the immune system. By studying the effects of physiological stress in the form of exercise, further discovery of the NK cell response in the context of human growth may provide unique insights into the mechanisms that regulate NK cell mobilization, maturation, and function. OBJECTIVES The long-term goal of my research program is to understand the effects of specific episodes of exercise on natural killer cells during human growth. My short-term objectives are to: 1. Characterize the effect of different types of exercise on NK cell subsets and function; 2. Quantify the effects of growth and maturation on exercise-induced changes in NK cell phenotype, which comprises NK subsets as well as NK receptor expression, density, and diversity; 3. Clarify the contributions of NK cell properties and the systemic environment to the NK cell response to acute exercise. METHODS Objective #1: Much of the literature in children has examined the effects of continuous exercise on NK cell subsets, but there is little evidence to inform NK cell function and how different types of exercise may regulate NK cells. Boys and girls will complete 4 distinct types of exercise in a randomized fashion. Pre- and post-exercise blood samples will be used to quantify NK cell subsets (CD56bright, and CD56dim), and function (cytotoxic activity per NK cell) by flow cytometry. Objective #2: I will use a longitudinal study design to examine the effects of growth and maturation on NK phenotype to further our understanding of sensitive growth phases whereby exercise may influence NK cell function. Pre and post pubertal boys and girls will be assessed annually over 4 years. Exercise-induced changes NK cells and NK receptor expression, density, and diversity with exercise and over time. Objective #3: The processes of NK cell maturation and mobilization are driven by an interaction between circulating NK cell properties and the systemic microenvironment. I will use in vitro experiments with samples collected in Objective #2 to examine the extent to which these contribute to the response to exercise. NK cells will be isolated from resting blood samples and incubated with post-exercise cell-free serum. A portion of each sample will be assessed by flow cytometry for NK cell phenotype, with the remaining co-cultured with target cells to induce NK cell cytotoxic activity.

自然杀伤(NK)细胞是一个动态的淋巴细胞亚群，驱动先天和获得性免疫反应。NK细胞是对急性运动最敏感的免疫细胞，运动是生理压力的一种形式。与年轻人相比，儿童和老年人对特定的运动时段表现出抑制的NK细胞反应。不幸的是，这些数据是基于横断面研究，很少同时检测NK细胞的功能。研究NK细胞的急性变化很重要，因为NK细胞数量和/或功能的下调可能会对免疫系统产生终结性的负面影响。通过研究运动形式的生理应激的影响，进一步发现人类生长背景下的NK细胞反应可能为调节NK细胞动员、成熟和功能的机制提供独特的见解。 目标 我的研究计划的长期目标是了解特定时间段的运动对人类生长过程中自然杀伤细胞的影响。我的短期目标是： 1.表征不同类型运动对NK细胞亚群和功能的影响； 2.量化生长和成熟对运动诱导的NK细胞表型变化的影响，包括NK细胞亚群以及NK受体的表达、密度和多样性； 3.明确NK细胞特性和系统环境对急性运动后NK细胞反应的影响。 方法 目的#1：许多儿童文献研究了持续运动对NK细胞亚群的影响，但很少有证据表明NK细胞的功能以及不同类型的运动如何调节NK细胞。男孩和女孩将以随机方式完成四种不同类型的运动。运动前和运动后的血样将用流式细胞仪测定NK细胞亚群(CD56bright和CD56dim)和功能(每个NK细胞的细胞毒活性)。 目的#2：我将采用纵向研究设计来研究生长和成熟对NK细胞表型的影响，以加深我们对运动可能影响NK细胞功能的敏感生长阶段的理解。青春期前和青春期后的男孩和女孩将在4年内每年接受评估。随着运动和时间的延长，运动诱导的NK细胞和NK受体的表达、密度和多样性发生变化。 目的#3：NK细胞的成熟和动员过程是由循环中的NK细胞特性和全身微环境相互作用驱动的。我将使用目标2中收集的样本进行体外实验，以检验这些因素对运动反应的影响程度。NK细胞将从静息血液样本中分离出来，并与运动后无细胞血清孵育。每个样本的一部分将通过流式细胞仪进行NK细胞表型的评估，其余的将与目标细胞共同培养以诱导NK细胞的细胞毒活性。