Role of prenatal stress-induced fetal neuro-immune rewiring in susceptibility to develop pediatric eczema

Introduction

The prenatal period is a critical timeframe during which all the physiological systems of the body, including immune and sensory systems, develop their specific functions and adapt to possible incoming cues. Atopic dermatitis, also known as “eczema,” is the most common skin manifestation in infants and toddlers from 3 months to 2 years of age, with a very early onset during the first years of life.

Background

While genetic and immune factors play an important role, recent epidemiological studies have listed prenatal stress as an important risk factor for allergic disorders. These studies associate prolonged exposure to high emotional strain during pregnancy with an increase in the offspring's susceptibility to develop eczema.

Project Aim

The proposed project aims to seek external factors that might influence the development of eczema in infants through the lenses of neuro-immunology.

Methodology

We wish to use sophisticated mouse models, single-cell transcriptomics, and whole-tissue imaging approaches to evaluate how a relevant model of non-infectious prenatal stress can predispose offspring to develop eczematous lesions that resemble pediatric atopic dermatitis.

Exploration of Mechanisms

We will then explore if the observed phenotype could be driven by in utero dysregulations of myeloid cells (in particular mast cells) and peripheral sensory neurons development, leading to the subsequent formation of abnormal skin neuro-immune units in offspring.

Proposed Work

To accomplish these goals, we have proposed a body of work that is solidly based on preliminary data, with four aims that will test innovative hypotheses by using informative transcriptomic approaches, as well as a new multiplexed imaging system that we recently developed.

Significance

This work will thus address significant gaps in our knowledge about how prenatal adverse events could set the stage toward the development of classical features of pediatric eczema. Most importantly, it should lead toward potential new therapeutic/preventive options for allergic disorders.