Anxiety in male psoriasis mouse model is mediated by the interaction between γδ T cell-derived IL-17A and microglia

Both clinical and animal studies indicate a high incidence of anxiety in psoriasis, though the underlying mechanisms remain poorly understood. Our previous review suggested that T cells, related cytokines, and blood-brain barrier (BBB) disruption might serve as potential links between the two conditions. This study aimed to investigate the mechanistic connection.

Psoriasis was induced in male C57BL/6J mice using imiquimod (IMQ). Anxiety-like behaviors were assessed through the open field test, elevated plus maze test, and light-dark box test. Microglial activation was evaluated by immunofluorescence and flow cytometry. Hippocampal inflammatory cytokine expression was measured by Western blot and qRT-PCR. Inflammatory factors in brain and periphery were flow cytometrically analyzed. BBB integrity was examined using Evans blue injection and tight junction protein expression. To elucidate the roles of microglia, IL-17A, and γδ T cells, each of them was separately depleted in psoriasis mouse models, with Tcrd^-/- mice used for verification.

IMQ-treated mice exhibited significant anxiety-like behaviors, increased pro-inflammatory (CD86⁺) microglial activation, elevated hippocampal IL-17A (mainly derived from γδ T cells), and impaired BBB integrity characterized by reduced ZO-1 and Occludin expression. Depletion of microglia, IL-17A, or γδ T cells significantly alleviated anxiety-like behaviors in psoriasis mouse models. Following microglial depletion, RORγt expression in brain γδ T cells decreased. Conversely, IL-17A neutralization or modeling on Tcrd^-/- mice altered microglial activation patterns.

Psoriasis mouse models exhibit anxiety-like behaviors accompanied by impaired BBB integrity. These effects are associated with γδ T cell-microglia interactions, in which IL-17A plays a crucial role.