Sympathetic nerve dysfunction exacerbates skin inflammation in atopic dermatitis - 28/02/26

Doi : 10.1016/j.jaci.2025.12.994

Su Yu, MD, PhD ^a,^{^{∗
These authors contributed equally to this work.}}, Yao Xu, MD, PhD ^a,^{^{∗
These authors contributed equally to this work.}}, Yizhen Li, MD ^a, Xiaoyu Pan, MD ^a, Zixin Zhao, BS ^a, Chaoying Gu, MD, PhD ^a, Huibin Yin, MD, PhD ^a, Qianwen Shan, BS ^a, Yuemeng Wu, MD, PhD ^a, Yu Wang, MD, PhD ^a, Hao Wu, MD, PhD ^a, Yehua Cai, MD, MS ^b, Xu Yao, MD, PhD ^c,^⁎ , Yan-Gang Sun, PhD ^d,^e,^⁎ , Wei Li, MD, PhD ^a,^⁎

^a Department of Dermatology, Shanghai Institute of Dermatology, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China

^b Department of Ultrasound, Huashan Hospital, Fudan University, Shanghai, China

^c Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China

^d Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China

^e State Key Laboratory of Brain Cognition and Brain-Inspired Intelligence Technology, Shanghai, China

^∗ Corresponding author: Wei Li, MD, PhD, Department of Dermatology, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Rd, Shanghai 200040, China. Department of Dermatology Huashan Hospital Fudan University 12 Wulumuqi Middle Rd Shanghai 200040 China ^∗∗ Yan-Gang Sun, PhD, Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China. Institute of Neuroscience Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences Shanghai 200031 China ^∗∗∗ Xu Yao, MD, PhD, Department of Allergy and Rheumatology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, 12 Jiangwangmiao St, Nanjing 210042, China. Department of Allergy and Rheumatology Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College 12 Jiangwangmiao St Nanjing 210042 China

Graphical abstract

Le texte complet de cet article est disponible en PDF.

Abstract

Background

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with severe itching, posing a great burden on both the physical and mental health of patients. AD is frequently complicated by sympathetic nervous system (SNS) dysfunction.

Objective

We sought to explore the interplay between skin inflammation and SNS activity during AD development.

Methods

Using clinical cohort data and murine models, we used impression mold technique, simultaneous noninvasive recording of electrocardiogram and skin sympathetic nerve activity, ultrasound, immunohistochemistry, and RNA sequencing to investigate the impact of AD inflammation on sympathetic function and structure. Conversely, chemogenetic manipulations were used to assess the effects of the SNS on AD-related inflammation and itch.

Results

We revealed significant SNS dysfunction in patients with AD, which was manifested by diminished perspiration and attenuated electrical responses, and ultrasound data showed compensatory hypertrophy in the sympathetic ganglia. These impairments were partially reversed in patients with AD treated with dupilumab. Moreover, MC903-induced AD-like dermatitis exhibited histologic and molecular indications of inflammatory stress and injury in the sympathetic ganglia. Chemogenetic inhibition of Phox2b ⁺ sympathetic neurons exacerbated MC903-induced cutaneous inflammation and itch sensation in mice, whereas targeted activation of sympathetic neurons attenuated both clinical and histologic manifestations of AD-like dermatitis.

Conclusions

Our data revealed a detrimental cycle between AD skin inflammation and sympathetic nerve dysfunction.

Le texte complet de cet article est disponible en PDF.

Key words : Atopic dermatitis, sympathetic nerve, skin inflammation, sympathetic ganglia, Phox2b

Abbreviations used : AAV, AD, CNO, DEG, EASI, H&E, hM3Dq, hM4Di, ILC2, IMT, MC903, NE, neuECG, 6-OHDA, Phox2b , SCG, SKNA, SNS, v.g.

Plan

Results

Functional and structural alterations in the SNS of patients with AD

Inflammatory stress and injury in the SNS in a mouse model of AD

Aggravation of AD-like dermatitis on chemogenetic inhibition of sympathetic neurons

Aggravation of AD inflammation by Phox2b ⁺ sympathetic neurons

Attenuation of AD inflammation after chemogenetic activation of Phox2b ⁺ sympathetic neurons

Discussion

Export

Vol 157 - N° 3

P. 677-692 - mars 2026 Retour au numéro

Article précédent

Targeting IL-22RA1 with temtokibart: A novel approach in atopic dermatitis: Phase 2a monotherapy study results
Diamant Thaçi, Vivian Laquer, Charles Lynde, Adam Reich, Weily Soong, Margitta Worm, Petra Arlert, Allan Blemings, Thomas Litman, Britta C. Martel, Martin Olesen, Ole E. Sørensen, Melinda Gooderham

| Article suivant

Resolution of epithelial dysfunction in eosinophilic esophagitis is mediated by an HIF-1α-CD73-adenosine signaling axis
Shauna K. Kellett, Taylor Crue, Sofia N. Almeida Cruz, Gary E. Markey, Sinéad Ryan, Louise Crowe, Olga Fagan, Niall Conlon, Claire L. Donohoe, Susan McKiernan, Glenn T. Furuta, Joanne C. Masterson

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.

Déjà abonné à cette revue ?

connectez-vous ou créez un compte

Sympathetic nerve dysfunction exacerbates skin inflammation in atopic dermatitis - 28/02/26

Graphical abstract

Abstract

Background

Objective

Methods

Results

Conclusions

Plan

Export citations

Fichier

Contenu

Accès rapides

Mon compte

Aide & support

Plateformes Elsevier Masson

Déclaration CNIL