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

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…