Predictors and determinants of pediatric immunity (Peds) - The unique characteristics of the human immune response in early life are critically important and yet remain poorly understood. Our overarching hypothesis is that the pediatric immune system is not just a naïve adult immune system but is fundamentally different. The challenges associated with pediatric studies, including small sample volumes and rare diseases, have been barriers to meaningful progress in the field, and there are numerous basic questions that remain unaddressed. By taking a synergistic multi-pronged approach, we aim to better understand the unique biology of pediatric immunity and its implications for normal immune function as well as a variety of disease states. The central hypothesis addressed in this program project is that genetics, developmental stage, and immune challenges shape the trajectories of antigen-specific and -agnostic homeostatic set points that determine future immune response quality and quantity. Our three projects, with support of our four cores, will synergize in addressing the following overarching and interconnected scientific aims. Aim 1: Uncover genetic and neonatal determinants of temporally ultra-stable, individualistic immune states established at infancy. Aim 2: Determine dynamic immune parameters remodeled throughout the pediatric age range by immune exposures, developmental variables, and genetics. Aim 3: Elucidate how baseline immune states predict and determine responses to immune challenges in an age-dependent manner in childhood. Our program will leverage multiple human subject cohorts that will offer important insights with broad relevance. Together, this work will enable us to construct a ‘growth chart’ of sorts for the pediatric immune system that will better enable identification and assessment of genetic, environmental, and developmental conditions that deviate immune trajectories into unhealthy ranges.
