Interleukin-17 Plays a Crucial Role in Atopic Dermatitis-Associated Blood-Brain Barrier Disruption and Cognitive Impairment

Atopic dermatitis increasingly demonstrates central nervous system involvement, including emotional disturbances and cognitive decline, although the underlying mechanisms remain poorly characterized.While peripheral tissue injury-driven CNS symptoms are often associated with blood-brain barrier disruption, whether BBB alterations contribute to AD-associated neuropathology and their mechanistic basis are unexplored. Eight days of calcipotriol exposure induced murine AD-like skin inflammation, triggering anxiety, depression, cognitive deficits, and significant BBB disruption. Neuroinflammation was confirmed by microglial and astrocytic hyperactivity. Cerebral vascular endothelial cells exhibited enhanced vesicular transport and disrupted tight junctions. Multi-omics integration revealed significant dysregulation of Interleukin-17signaling. Administration of anti-mouse IL-17A antibody to mice ameliorated cutaneous pathology, attenuated BBB disruption, suppressed neuroinflammation, and rescued behavioral abnormalities. These results established IL-17 as a central mediator of AD-related CNS complications, providing a therapeutic framework for clinical intervention.