A sympathetic-eosinophil axis orchestrates psychological stress to exacerbate skin inflammation

• 成果类型: Article
• 署名作者: Tian, Jiahe; Cao, Yudian; Li, Yilei; Sun, Junlong; Zhan, Cheng; Ni, Wei; Zheng, Yongjun; Wang, Yanqing; Liu, Shenbin
• 署名单位: Fudan University; Fudan University; Fudan University; Fudan University; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Fudan University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adv5974
• 发表日期: 2026-03-19
• 关键词: CATIONIC PROTEIN; SALMETEROL; mice; identification; diversity; receptor; GANGLIA; neurons; blood; MODEL

摘要

Psychological stress is believed to exacerbate dermatitis, yet the neurobiological mechanisms linking stress to immune processes remain elusive. We identified a subset of prodynorphin-positive (Pdyn+) noradrenergic sympathetic neurons in mice that specifically innervate hairy skin, mediating stress-induced exacerbation of skin inflammation in an eosinophil-dependent manner. Genetic ablation of Pdyn+ sympathetic neurons or eosinophils mitigated stress-evoked worsening of inflammation in atopic dermatitis-like mice, whereas optogenetic activation of these neurons precipitated inflammation through eosinophils. Pdyn+ sympathetic neurons recruited eosinophils through the CCL11-CCR3 axis and activated them through the adrenergic receptor beta2 (Adrb2) in inflamed skin. Our findings reveal a neuroimmunological mechanism underlying psychological stress-induced exacerbation of dermatitis, emphasizing the Pdyn+ sympathetic-eosinophil axis as a crucial interface between the brain and skin inflammation, with potential therapeutic implications.