Decoding mechanisms of early life inflammation

Icahn School Of Medicine At Mount Sinai, New York NY

Investigators

Abstract

One in four children in the Western world develop atopic dermatitis (AD), a devastating inflammatory skin disorder, often appearing as early as 8 weeks after birth. Existing therapies targeting show limited efficacy in young children, highlighting the need for interventions tailored to early life. Yet, how the early life immune system responds to allergens is poorly understood. This research project aims to elucidate the innate and adaptive mechanisms governing neonatal immune responses and investigate how the innate immune system detects and mediates sterile inflammation during this critical developmental stage. We developed a novel mouse model of allergen-induced neonatal sterile inflammation, to prove mechanisms controlling immunity in this developmental window. In so doing, we uncovered heightened innate and adaptive immune responses in neonates compared to adults. Preliminary findings show neonatal dendritic cells (DCs) exhibit a unique "promiscuous" activation state, and Type 17 cells active directly in the skin, suggesting heightened reactivity in neonatal skin. In this application we will study the cellular and molecular mechanisms of heighted early-life immune system that underlie neonatal propensity for inflammation. This knowledge will have profound implications for the development of targeted therapeutics and preventive strategies against early-life sterile inflammation. Additionally, our research will contribute to a fundamental understanding of the mechanisms of neonatal immunity, with broad applications in early life immunization and anti-pathogen immunity.