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

Nadine Serhan, Nasser S. Abdullah, Nadine Gheziel, Alexia Loste, Rüçhan Ekren, Elodie Labit, Anne-Alicia Gonzalez, Giulia Oliva, Pauline Tarot, Camille Petitfils, Gaëlle Payros, Paolo D’Avino, Allison Voisin, Holly Freya Grace Tinsley, Rebecca Gentek, Carole Brosseau, Marie Bodinier, Laurent Reber, Pierre Val, Cezmi A. Akdis, Yasutaka Mitamura, Anand Kumar Andiappan, Jerry Kok Yen Chan, Florent Ginhoux, Amaury François, Nicolas Cénac, Lilian Basso and Nicolas Gaudenzio ()
Additional contact information
Nadine Serhan: Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) INSERM UMR1291 – CNRS UMR5051 – University of Toulouse
Nasser S. Abdullah: Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) INSERM UMR1291 – CNRS UMR5051 – University of Toulouse
Nadine Gheziel: Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) INSERM UMR1291 – CNRS UMR5051 – University of Toulouse
Alexia Loste: Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) INSERM UMR1291 – CNRS UMR5051 – University of Toulouse
Rüçhan Ekren: Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) INSERM UMR1291 – CNRS UMR5051 – University of Toulouse
Elodie Labit: Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) INSERM UMR1291 – CNRS UMR5051 – University of Toulouse
Anne-Alicia Gonzalez: Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) INSERM UMR1291 – CNRS UMR5051 – University of Toulouse
Giulia Oliva: INSERM
Pauline Tarot: INSERM
Camille Petitfils: UPS
Gaëlle Payros: UPS
Paolo D’Avino: University of Zurich
Allison Voisin: iGRED
Holly Freya Grace Tinsley: University of Edinburgh
Rebecca Gentek: University of Edinburgh
Carole Brosseau: l’Alimentation et l’Environnement
Marie Bodinier: l’Alimentation et l’Environnement
Laurent Reber: Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) INSERM UMR1291 – CNRS UMR5051 – University of Toulouse
Pierre Val: iGRED
Cezmi A. Akdis: University of Zurich
Yasutaka Mitamura: University of Zurich
Anand Kumar Andiappan: Singapore Immunology Network, Agency for Science, Technology and Research
Jerry Kok Yen Chan: KK Women’s and Children’s Hospital
Florent Ginhoux: Singapore Immunology Network, Agency for Science, Technology and Research
Amaury François: INSERM
Nicolas Cénac: UPS
Lilian Basso: Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) INSERM UMR1291 – CNRS UMR5051 – University of Toulouse
Nicolas Gaudenzio: Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) INSERM UMR1291 – CNRS UMR5051 – University of Toulouse

Nature, 2025, vol. 646, issue 8083, 161-170

Abstract: 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 constraints1,2. Although epidemiological studies have suggested an association between PS and a higher risk of eczema in children3–6, 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+ 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.

Date: 2025
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DOI: 10.1038/s41586-025-09419-8

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