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

Project description

Studying the link between prenatal stress and infant eczema

During pregnancy, stress can harm unborn babies, increasing their risk of eczema, a common skin condition in infants. If this stress is prolonged, it may alter how babies’ immune and sensory systems develop, potentially leading to eczema early in life. In this context, the ERC-funded PRENATALL project will use advanced techniques, such as mouse models and cell analysis, to explore how prenatal stress influences eczema development in infants. By studying the underlying mechanisms, the project seeks to uncover new ways to prevent and treat eczema in children. Armed with preliminary data and innovative approaches, PRENATALL will pave the way for novel therapeutic strategies. It also holds promise for addressing the root causes of allergic disorders.

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.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2023-COG

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Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 857 135,00
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 857 135,00

Beneficiaries (1)

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