Maternal stress triggers early-life eczema through fetal mast cell programming

Prenatal stress (PS) is a repeated exposure to aversive situations during pregnancy, including high emotional strain, which is suspected to affect homeostatic systems in infants. Paediatric eczema develops quickly after birth at flexural sites subjected to continuous mechanical constraints<sup>1,2</sup>. Although epidemiological studies have suggested an association between PS and a higher risk of eczema in children<sup>3-6</sup>, no causative biological link has yet been identified. Here we show that eczema at birth originates from molecular dysregulations of neuroimmune circuits in utero, triggered by fluctuations in the maternal hypothalamic-pituitary-adrenal axis. We found that offspring of stressed pregnant dams have dysregulated mast cells and skin-projecting neurons and quickly develop eczema in response to harmless mechanical friction. We demonstrated that PS transiently modulates amniotic fluid corticosterone concentrations, which directly alters the activation program of skin mast cells expressing the glucocorticoid receptor Nr3c1 and the adjacent sensory neurons conveying mechanosensation. Therapeutic normalization of maternal corticosterone concentrations or genetic depletion of Mcpt5<sup>+</sup> mast cells during stressed gestation prevents fetal immune dysregulation and protects against eczema development after birth. Our findings support a new model in which early-onset paediatric eczema originates from dysregulations in the fetal immune system, caused by fluctuations in maternal glucocorticoids induced by stress.

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Journal
Nature
Published
2025-08-27
DOI
https://doi.org/10.1038/s41586-025-09419-8
Citations
11
Primary Topic
IL-33, ST2, and ILC Pathways
Type
article
Field-Weighted Citation Impact
8.77
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article

Maternal stress triggers early-life eczema through fetal mast cell programming

Nicolas Gaudenzio, Pierre Val, Nicolas Cénac, Elodie Labit et al.
11 citations
Nature
IL-33, ST2, and ILC Pathways
8.77
article

Maternal stress triggers early-life eczema through fetal mast cell programming

Nicolas Gaudenzio, Pierre Val, Nicolas Cénac, Elodie Labit, Gaëlle Payros, Lilian Basso, Marie Bodinier, Jerry Kok Yen Chan, Giulia Oliva, Paolo D’Avino, Anand Kumar Andiappan, Laurent L. Reber, Carole Brosseau, Allison Voisin, Florent Ginhoux, Yasutaka Mitamura, Nadine Serhan, Cezmi A. Akdiş, Amaury François, Alexia Loste, Camille Petitfils, Rebecca Gentek, Anne‐Alicia Gonzalez, Rüçhan Ekren, Nadine Ghéziel, Holly Tinsley, Nasser Abdullah, Pauline Tarot
article en
11 citations

Abstract

Prenatal stress (PS) is a repeated exposure to aversive situations during pregnancy, including high emotional strain, which is suspected to affect homeostatic systems in infants. Paediatric eczema develops quickly after birth at flexural sites subjected to continuous mechanical constraints<sup>1,2</sup>. Although epidemiological studies have suggested an association between PS and a higher risk of eczema in children<sup>3-6</sup>, no causative biological link has yet been identified. Here we show that eczema at birth originates from molecular dysregulations of neuroimmune circuits in utero, triggered by fluctuations in the maternal hypothalamic-pituitary-adrenal axis. We found that offspring of stressed pregnant dams have dysregulated mast cells and skin-projecting neurons and quickly develop eczema in response to harmless mechanical friction. We demonstrated that PS transiently modulates amniotic fluid corticosterone concentrations, which directly alters the activation program of skin mast cells expressing the glucocorticoid receptor Nr3c1 and the adjacent sensory neurons conveying mechanosensation. Therapeutic normalization of maternal corticosterone concentrations or genetic depletion of Mcpt5<sup>+</sup> mast cells during stressed gestation prevents fetal immune dysregulation and protects against eczema development after birth. Our findings support a new model in which early-onset paediatric eczema originates from dysregulations in the fetal immune system, caused by fluctuations in maternal glucocorticoids induced by stress.

NatureVol. 646(8083)
Agency for Science, Technology and Research (SG), Centre National de la Recherche Scientifique (FR), Université Toulouse III - Paul Sabatier (FR), Inserm (FR), École Nationale Vétérinaire de Toulouse (FR), Université Fédérale de Toulouse Midi-Pyrénées (FR), Université de Montpellier (FR), University of Zurich (CH), Singapore Immunology Network (SG), Institut Gustave Roussy (FR), SingHealth Duke-NUS Academic Medical Centre (SG), Toulouse Mathematics Institute (FR), Biopolymères Interactions Assemblages (FR), KK Women's and Children's Hospital (SG), MRC Centre for Reproductive Health (GB), Institut de Recherche en Santé Digestive (FR), Duke-NUS Medical School (SG), Centre Hospitalier Universitaire de Clermont-Ferrand (FR), Institut des Maladies Métaboliques et Cardiovasculaires (FR), Institut de Génomique Fonctionnelle (FR), University of Edinburgh (GB)
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Openalex Percentile: Top 2%
IL-33, ST2, and ILC Pathways
8.77
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