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

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

  • Neuropharmacology. 2026 Jun 1:290:110908. doi: 10.1016/j.neuropharm.2026.110908.
Juexi Yang 1,  Song Zhang 2,  Cuiying Fu 1,  Yan Dai 1,  Yan Sun 1,  Xiaoke Dou 1,  Yun Lin 3,  Yan Wu 4
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China.
  • 2 Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 3 Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China. Electronic address: [email protected].
  • 4 Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address: [email protected].
PMID: 41780818 DOI: 10.1016/j.neuropharm.2026.110908
Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords

Anxiety; Blood-brain barrier; IL-17A; Microglia; Psoriasis; γδ T cell.

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