📋 Tender Overview
Role Of Prenatal Stress-Induced Fetal Neuro-Immune Rewiring In Susceptibility To Develop Pediatric Eczema
Funded Under
European Research Council (Erc)
Total Cost
€ 2 857 135,00
Eu Contribution
€ 2 857 135,00
Coordinated By
Institut National De La Sante Et De La Recherche Medicale
France
Objective
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. While genetic and immune factors play an important role, recent epidemiological studies have listed prenatal stress as an important risk factor of allergic disorders, and associated prolonged exposure to high emotional strain during pregnancy to an increase in the offspring susceptibility to develop eczema. The proposed project aims to seek external factors that might influence the development of eczema in infants through the lenses of neuro-immunology.
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. 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 and subsequent formation of abnormal skin neuro-immune units in offspring.
To accomplish these goals, we have proposed herein 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. 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 and, most importantly, should lead toward potential new therapeutic/preventive options for allergic disorders.
