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Sympathetic nerve dysfunction exacerbates skin inflammation in atopic dermatitis.

Su Yu1, Yao Xu1, Yizhen Li1

  • 1Department of Dermatology, Shanghai Institute of Dermatology, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.

The Journal of Allergy and Clinical Immunology
|December 25, 2025
PubMed
Summary

Atopic dermatitis (AD) involves sympathetic nervous system (SNS) dysfunction, worsening inflammation and itch. Targeting SNS activity can reduce AD symptoms, suggesting a link between skin and nerve health.

Keywords:
Atopic dermatitisPhox2bskin inflammationsympathetic gangliasympathetic nerve

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Area of Science:

  • Dermatology and Neuroscience
  • Neuroimmunology

Background:

  • Atopic dermatitis (AD) is a chronic inflammatory skin condition causing significant patient burden.
  • AD is often associated with dysfunction of the sympathetic nervous system (SNS).

Purpose of the Study:

  • To investigate the relationship between skin inflammation and SNS activity in AD.
  • To understand how SNS dysfunction impacts AD development and how SNS modulation affects AD.

Main Methods:

  • Clinical data and mouse models were used, employing techniques like neuECG, ultrasound, and immunohistochemistry.
  • Chemogenetic manipulation assessed the impact of SNS on AD inflammation and itch.
  • RNA sequencing and impression mold technique (IMT) were utilized.

Main Results:

  • AD patients showed SNS dysfunction (e.g., reduced perspiration) and sympathetic ganglia hypertrophy, partially improved by dupilumab.
  • AD-like dermatitis in mice led to sympathetic ganglia inflammation and injury.
  • Inhibiting specific sympathetic neurons worsened AD symptoms, while activating them reduced AD severity.

Conclusions:

  • A detrimental feedback loop exists between AD skin inflammation and sympathetic nerve dysfunction.
  • Modulating SNS activity shows therapeutic potential for AD.