Comparative analysis of cutaneous features of psoriasis in acute and chronic imiquimod-induced mouse models

Psoriasis is a chronic inflammatory skin disorder influenced by genetic and environmental factors. The imiquimod (IMQ)-induced mouse model is widely used to study psoriasis-like skin inflammation. However, its current use is largely limited to short treatment periods. Therefore, this model predominantly reflects acute inflammation and is limited in its capacity to capture the chronic nature of psoriasis. To date, little attention has been given to the extension of IMQ treatment duration to study the characteristics of sustained inflammation. This study aimed to provide the first direct comparison between short-term (ST, 4 days) and long-term (LT, 9 weeks) IMQ treatments on cutaneous histological, molecular and functional psoriasis features and to assess their similarity with human psoriasis. Both models demonstrated similar global severity, but with distinct features: ST-IMQ treatment led to increased epidermal hyperplasia and impaired skin barrier function, while LT-IMQ treatment was associated with greater desquamation and impaired suprabasal differentiation. Dermal mechanical properties and endothelial dysfunction were similar between the two models. Gene expression analysis revealed differentially expressed psoriasis-related markers between ST- and LT-IMQ treatments, with both models showing similarities to human psoriasis. These findings offer critical insights into how acute and chronic models can be tailored to study specific psoriasis features.