New research leveraging patient data and mouse models reveals how psychological stress can worsen atopic dermatitis, or eczema. It does so by activating a specific neural pathway that links the brain to immune responses in the skin. The study's authors emphasize that managing psychological stress, alongside conventional therapies, may represent an underused but potentially powerful strategy for improving outcomes in eczema. "[The authors] offer a mechanistic explanation for the well-documented but poorly understood link between stress and atopic dermatitis flare-ups," write Nicolas Gaudenzio and Lillan Basso in a related Perspective. "Research into the existence of similar mechanisms in other stress-sensitive inflammatory diseases, such as psoriasis or inflammatory bowel disease, is also needed," they say. Psychological stress is known to disrupt the body's immune balance. The skin is particularly vulnerable because it contains dense networks of nerves and immune cells, making it highly responsive to stress-related signals. Conditions such as eczema illustrate this neurobiological connection, as stress frequently exacerbates the condition. Recent studies suggest that stress signals transmitted through the sympathetic nervous system may directly influence immune activity in the skin. Moreover, eosinophils – immune cells that release inflammatory proteins and cytokines – are closely linked to dermatitis severity. However, the mechanisms by which stress-driven neural signals recruit and activate these cells remain poorly understood.
To address this gap, Jiahe Tian and colleagues analyzed clinical data from 51 eczema patients and complementary mouse models to examine the relationship between stress and inflammatory immune responses in the skin. Tian et al. identified a subset of prodynorphin-positive (Pdyn)+ noradrenergic sympathetic neurons that preferentially innervate hairy skin. Using genetic ablation and optogenetic activation, the authors tested how these neurons influence inflammation and eosinophil activity and found that higher stress in patients correlated with increased eosinophil accumulation in the skin. In mouse models, Tian et al. show that Pdyn+ sympathetic neurons transmitted stress signals from the brain to the skin, worsening inflammation. These neurons recruited eosinophils through the CCL11–CCR3 signaling pathway and activated them through the beta-2 adrenergic receptor. Removing either these neurons or eosinophils reduced stress-induced inflammation, while activating the neurons increased it.
