Jiahe Tian, Yudian Cao, Yilei Li, Junlong Sun, Cheng Zhan, Wei Ni, Yongjun Zheng, Yanqing Wang, Shenbin Liu
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.