INITIALISE: Inflammation in human early life: targeting impacts on life-course health

初始化：人类早期生命中的炎症：针对生命全程健康的影响

• 批准号: 10044835
• 金额: $ 49.79万
• 依托单位: UNIVERSITY OF ABERDEEN
• 依托单位国家: 英国
• 项目类别: EU-Funded
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10044835
• 关键词: INITIALISE; Inflammation; human; early; life

The development of the human immune system in early life, including in utero, impacts the risks of several diseases later in life, particularly immune-mediated diseasessuch as allergies, asthma, and autoimmunity. Yet, the mechanisms of early life immune imprinting have been poorly understood in humans due to the difficulty in obtaining samples and the challenges of deriving the most important data from small sample volumes available. Furthermore, these studies are complicated by the many simultaneous exposures with potential impact on developing immune cells, colonising microbes, and immune-microbe mutualism. To better understand such interactions, a combinations of large population studies with longitudinal data and long-term follow-up and more detailed studies in smaller sets of children will be needed. Here we propose such a combined and interdisciplinary approach by intersecting multiple cohorts and existing biobanks, applying state-of the art technologies for exposure analyses and immune system investigation. This will enable us to understand the environmental factors shaping human immune systems early in life, their mechanisms of action, and impact on life-course health. The specific objectives of INITIALISE are: 1. to elucidate how exposures and genome impact gut microbiome, host immune system and metabolism, and how the interplay of these factors impact life-course health. 2. to define the role of the maturation of the immune system as a mediator between exposures and life-course health. Functional studies will be performed, to test specific mechanisms of environmental factors differing among children with different health outcomes and their imprinting on developing immune cells. 3. to perform a pilot clinical study, targeting the immune system, for personalised disease prevention. 4. to set up a collaborative data science platform for the studies of early-life factors linked with life-course health.no project summary.

人类免疫系统在早期（包括子宫内）的发展会影响生命后期几种疾病的风险，尤其是免疫介导的疾病，例如过敏，哮喘和自身免疫性。然而，由于难以获得样品的困难以及从可用的小样本量中获取最重要的数据的挑战，因此人类的早期免疫印迹的机制在人类中已经很糟糕。此外，这些研究对许多同时暴露，对发展免疫细胞，定居微生物和免疫微生物互助的潜在影响使这些研究变得复杂。为了更好地了解这种相互作用，将需要在纵向数据和长期随访以及对较小儿童组中的更详细研究的大量人群研究组合。在这里，我们通过与多个同类和现有的生物库相交，提出了这种合并和跨学科的方法，应用最先进的技术进行暴露分析和免疫系统调查。这将使我们能够理解生命早期人类免疫系统的环境因素，其行动机理以及对生活道路健康的影响。初始化的具体目标是：1。阐明暴露和基因组如何影响肠道微生物组，宿主免疫系统和代谢以及这些因素的相互作用如何影响生命过程的健康。 2。将免疫系统成熟的作用定义为暴露与生命过程之间的介体。将进行功能研究，以测试患有不同健康结果的儿童不同及其在发展免疫细胞上的印迹的环境因素的特定机制。 3。进行针对免疫系统的试点临床研究，以预防个性化疾病。 4。建立一个协作数据科学平台，以研究与生活课程健康有关的早期生活因素的研究。没有项目摘要。