Dissecting the role of imiquimod and isostearic acid in Aldara-induced psoriasis mouse model.

Aldara (5% imiquimod with 25% isostearic acid [ISA]) cream-induced psoriasiform inflammation is a widely used mouse model to study psoriasis. Imiquimod is a toll-like receptor 7 (TLR7) agonist; however, the role of TLR7 signaling in human psoriasis is unclear. We studied the requirement of TLR7 signaling in Aldara-induced psoriasis and examined the ability of ISA to induce psoriasis in a TLR7-independent manner. C57BL/6J mice were treated with (i) Vaseline, (ii) ISA in Vaseline, (iii) Aldara, (iv) oleic acid in Vaseline, or (v) generic imiquimod formulated with oleic acid. ISA alone did not increase psoriasis-related cytokines or plasmacytoid dendritic cell infiltration into the dorsal skin and failed to induce phenotypic and histological changes of psoriasis. Oleic acid also did not induce significant erythema and scaling, acanthosis, or systemic changes. Imiquimod formulated with either ISA or oleic acid induced psoriasis in vivo. Mechanistically, stimulation of plasmacytoid dendritic cells with ISA did not induce NF-κB activation or inflammatory cytokine expression. Our findings suggest that ISA alone is insufficient to induce psoriasis in vivo or NF-κB-dependent inflammatory cytokines in vitro. This work highlights the critical role of TLR7 signaling in Aldara-induced psoriasis pathogenesis, suggesting that further studies on its direct role in human psoriasis are warranted.