INITIALISE

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 diseases such 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.

2023

2028