图卢兹传染病和炎症性疾病研究所Nicolas Gaudenzio小组取得一项新突破。他们的最新研究揭示了母亲的压力通过胎儿肥大细胞编程引发早期湿疹。该项研究成果发表在2025年8月27日出版的《自然》上。

本研究表明，出生时的湿疹源于子宫内神经免疫回路的分子失调，由母体下丘脑-垂体-肾上腺轴的波动引发。研究人员发现，应激孕鼠的后代肥大细胞和皮肤突出神经元失调，并迅速发展为湿疹，以响应无害的机械摩擦。研究团队证明，PS可瞬时调节羊水皮质酮浓度，从而直接改变表达糖皮质激素受体Nr3c1和传递机械感觉的相邻感觉神经元的皮肤肥大细胞的激活程序。应激妊娠期间母体皮质酮浓度的治疗性正常化或Mcpt5⁺肥大细胞的遗传耗竭可防止胎儿免疫失调并防止出生后发生湿疹。他们的发现支持了一种新的模型，即早发性儿科湿疹起源于胎儿免疫系统失调，由压力引起的母体糖皮质激素波动引起。

据悉，产前压力（PS）是指在怀孕期间反复暴露在令人厌恶的环境中，包括高情绪紧张，这被认为会影响婴儿的体内平衡系统。儿童湿疹在出生后受到持续机械约束的屈曲部位迅速发展。尽管流行病学研究表明PS与儿童湿疹高风险之间存在关联，但尚未发现因果生物学联系。

附：英文原文

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

Author: Serhan, Nadine, Abdullah, Nasser S., Gheziel, Nadine, Loste, Alexia, Ekren, Rhan, Labit, Elodie, Gonzalez, Anne-Alicia, Oliva, Giulia, Tarot, Pauline, Petitfils, Camille, Payros, Galle, DAvino, Paolo, Voisin, Allison, Tinsley, Holly Freya Grace, Gentek, Rebecca, Brosseau, Carole, Bodinier, Marie, Reber, Laurent, Val, Pierre, Akdis, Cezmi A., Mitamura, Yasutaka, Andiappan, Anand Kumar, Chan, Jerry Kok Yen, Ginhoux, Florent, Franois, Amaury, Cnac, Nicolas, Basso, Lilian, Gaudenzio, Nicolas

Issue&Volume: 2025-08-27

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 children3,4,5,6, 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.

DOI: 10.1038/s41586-025-09419-8

Source: https://www.nature.com/articles/s41586-025-09419-8