Secondary Exposure to IMQ or Irritants Enhances Psoriasiform Recurrence Through Inflammatory Memory

Psoriasis relapse is frequently characterized by more pronounced inflammatory responses compared to the initial onset; however, the underlying mechanisms that drive disease recurrence remain poorly understood. This study aims to investigate whether secondary cutaneous exposure to imiquimod (IMQ) or other irritants exacerbates psoriasiform inflammation through the phenomenon of inflammatory memory. BALB/c mice were initially treated with IMQ to induce psoriasiform dermatitis, followed by a recovery period. Subsequently, secondary challenges were administered using IMQ, 12-O-tetradecanoylphorbol-13-acetate (TPA), or sodium dodecyl sulfate (SDS). Disease severity was evaluated through clinical scoring, histopathological changes (H&E staining), and immunohistochemical markers. Cytokine levels in the serum and lesional skin were quantified via ELISA, protein expression was analyzed via Western blotting, and gene expression was assessed via RT‒qPCR. Secondary stimulation resulted in significantly more severe skin inflammation compared to the initial exposure, as evidenced by greater clinical severity scores, increased epidermal thickness, enhanced inflammatory cell infiltration, and elevated expression levels of IL-17 A, TNF-α, and additional markers. This exacerbation was observed regardless of whether the secondary challenge was conducted with IMQ or alternative irritants, suggesting the presence of cross-stimulus inflammatory memory in the skin. Repeated cutaneous exposure to IMQ or irritants aggravates psoriasiform inflammation through inflammatory memory. These findings establish a valuable experimental model for studying the mechanisms of disease relapse and evaluating potential therapeutic interventions.