2. Academic Validation
  3. Hyperactivation of sympathetic nerves fuels basophil infiltration in atopic dermatitis

Hyperactivation of sympathetic nerves fuels basophil infiltration in atopic dermatitis

  • Immunity. 2026 Mar 10;59(3):598-617.e11. doi: 10.1016/j.immuni.2026.01.010.
Xinyang Xie 1,  Wenjing Jiang 1,  Lerong Lun 1,  Xiaobao Huang 1,  Rui Xu 1,  Xiuwen Li 2,  Jipang Zhan 3,  Yalin Xie 4,  Maoqia Shen 5,  Xinran Li 5,  Xin Yan 1,  Xiru Tang 1,  Rui Tang 4,  Yali Gao 1,  Wanying Zhai 1,  Huilin Su 1,  Xin Luo 6,  Jiande Han 1,  Christoph S N Klose 7,  Fengxian Li 8,  Fang Wang 9
Affiliations

Affiliations

  • 1 Department of Dermatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
  • 2 Institute for STDs/Leprosy Control and Prevention, Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong 510091, China.
  • 3 Department of Dermatologic Surgery, Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong 510091, China.
  • 4 Department of Dermatology, Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong 510091, China.
  • 5 Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
  • 6 Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong 510515, China.
  • 7 Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Microbiology, Infectious Diseases and Immunology, Hindenburgdamm 30, 12203 Berlin, Germany; Cluster of Excellence ImmunoPreCept, Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • 8 Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China. Electronic address: [email protected].
  • 9 Department of Dermatology, Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong 510091, China. Electronic address: [email protected].
PMID: 41722568 DOI: 10.1016/j.immuni.2026.01.010
Abstract

Emotional stress exacerbates atopic dermatitis (AD) and contributes to overall disease burden. While sympathetic nervous system (SNS) activity broadly interacts with emotional states, its role in skin immunity remains underexplored. Using a murine model of AD-like disease, we demonstrated that skin inflammation triggered anxiety-like behaviors and hyperactivation of peripheral SNS innervating the affected skin. Disruption of peripheral SNS signaling, either by denervation or anxiety-relief interventions, markedly attenuated skin inflammation. Mechanistically, basophils were identified as key effector cells regulated by SNS activity. Norepinephrine activated β2-adrenergic receptors to enhance basophil motility and the chemokine C-C motif chemokine ligand (CCL)6-C-C motif Chemokine Receptor (CCR)1 axis, thereby promoting skin inflammation. In human AD, sympathetic nerve remodeling was observed in skin lesions, and basophil-associated CCL23 (the human ortholog of murine CCL6) and CCR1 correlated with disease severity. These findings define an SNS-basophil axis that links emotional states to skin inflammation, highlighting autonomic regulation as a therapeutic target for chronic skin diseases.

Keywords

adrenergic receptor; anxiety; atopic dermatitis; basophil; chemokine; norepinephrine; skin inflammation; sympathetic nervous system.

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