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

人类早期免疫系统的发育，包括在子宫内，影响着后来生活中几种疾病的风险，特别是免疫介导的疾病，如过敏、哮喘和自身免疫。然而，由于获取样本的困难以及从小样本中获得最重要的数据的挑战，早期生命免疫印记的机制在人类中一直知之甚少。此外，这些研究由于许多同时暴露而变得复杂，可能会对免疫细胞的发育、微生物的定植和免疫-微生物的互惠关系产生影响。为了更好地了解这种相互作用，需要将大规模人口研究与纵向数据相结合，并对较小的儿童群体进行长期跟踪和更详细的研究。在这里，我们提出了这样一种综合和跨学科的方法，通过交叉多个队列和现有的生物库，应用最先进的技术进行暴露分析和免疫系统调查。这将使我们能够了解在生命早期塑造人类免疫系统的环境因素，它们的作用机制，以及对生命过程健康的影响。Initialise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、宿主免疫系统和新陈代谢，以及这些因素的相互作用如何影响生命过程的健康。2.确定免疫系统的成熟作为暴露与生命过程健康之间的中介的作用。将进行功能研究，以测试环境因素在不同健康结果的儿童中不同的具体机制及其对发育中的免疫细胞的影响。3.进行针对免疫系统的试验性临床研究，以个性化疾病预防为目标。4.建立与生命过程健康相关的早期生命因素研究的协作数据科学平台。无项目摘要。

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.