Work

A stress-responsive neurovascular axis shapes skin immune accessibility

Year: 2026

Type: article

Abstract: The skin is a highly innervated and vascularized organ that acts as a frontline sensor of environmental and internal physiological cues. While psychological stress and prolonged ultraviolet (UV) exposure aggravate inflammatory skin conditions, the underlying mechanisms remain elusive. Here, we identify a neurovascular mechanism whereby stress-induced sympathetic hyperactivation compromises vascular barrier integrity in the skin. Using surgical or chemical denervation, optogenetics, intravital imaging, and genetic models, we show that both acute psychological stress and high-dose UV exposure activate the skin sympathetic nervous system, triggering norepinephrine release and α2B-adrenergic receptor signaling in dermal endothelial cells. This pathway leads to RhoA/ROCK-mediated Claudin-5 disruption, resulting in increased vascular permeability and heightened immune cell infiltration. Pharmacological or genetic inhibition of this axis restores vascular stability and attenuates inflammation. These findings reveal that skin vasculature decodes sympathetic tone, highlighting potential therapies for stress-aggravated skin disorders.

Source: iScience

DOI: 10.1016/j.isci.2026.115122