Objective To explore the effects of different immune cells and nonimmune factors on the pathogenesis of psoriasis. Methods Balb / c mice, nude mice and NOG mice were each divided into a blank group and model group, with 10 mice in each group. In the model groups, imiquimod was applied to the back skin of the mice to induce a psoriasis- like model, and samples of the skin and spleen were taken after the last application of imiquimod. The pathological changes to the skin and spleen induced by imiquimod were observed, and skin inflammatory factors and energy metabolic factors of the skin and spleen were detected. Results Compared with the normal group, the skin appearance and pathological tissue of the model group in all three mouse types showed psoriasis-like lesions, and the levels of inflammatory factors ( IL6, IL17, IL22 and IL23) were significantly higher. In the model groups, the spleen was swollen for all three mouse types, and the pathological spleen section exhibited a larger white pulp area and higher amount of lymphocytes compared with the blank groups in the Balb / c mice and nude mice. The activities of Na⁺K⁺ -ATPase and Ca²⁺ Mg²⁺ -ATPase in the skin and spleen were lower in the model groups. The relative severity of the three models was as follows: Balb / c mice > nude mice > NOG mice. Conclusions Immune cell activation, especially T-cell activation, plays a key role in the pathogenesis of psoriasis, but psoriasis can still be induced in animals with a severe immune deficiency. A decrease in ATPase activity, which is a non-immune factor, may also be an inducing factor of psoriasis.