Interleukin-17 plays a crucial role in atopic Dermatitis-Associated Blood-Brain barrier disruption and cognitive...

Atopic dermatitis (AD) increasingly demonstrates central nervous system (CNS) 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 (BBB) disruption, whether BBB alterations contribute to AD-associated neuropathology and their mechanistic basis are unexplored. Eight days of calcipotriol(MC903) exposure induced murine AD-like skin inflammation, triggering anxiety, depression, cognitive deficits, and significant BBB disruption. The occurrence of neuroinflammation in AD mice was confirmed by observed morphological changes in microglia and astrocytes. Cerebral vascular endothelial cells exhibited enhanced vesicular transport and disrupted tight junctions. Multi-omics integration (brain transcriptomics and blood proteomics) revealed significant dysregulation of Interleukin-17 (IL-17) signaling. In vitro studies demonstrated that IL-17A impairs bEnd.3 cell activity and tight junction protein expression. 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.