Objective TET2 knockout(TET2-/-)mouse model was used to explore the impact of TET2 mutations on imiquimod(IMQ)induced psoriatic skin inflammation. Methods Mice were randomly divided into a wild-type(WT)control group,WT model group,TET2-/- control group and TET2-/- model group. IMQ-induced established the psoriasis-like dermatitis model. During the modeling period,the degree of skin lesions and pathological changes of mice in the WT group and TET2-/- model group were observed and compared daily. The mice were sacrificed when the phenotype reached the peak,and the spleen index of the four groups of mice was recorded. Using RT-qPCR to detect the expression levels of inflammatory factors TNF-α,IL-6,IL-17A,and IL-23 mRNA in mouse back lesions. Skin pathological sections were made and HE staining was used to compare the histopathological changes of the skin. Immunohistochemistry was performed to detect the expression of IL-17,INF-γ,and TNF-α in the back skin of mice in the four groups. The ultrastructure of the dermis and epidermis of mice in four groups was observed using transmission electron microscopy. Results TET2 expression is down-regulated in skin lesions of WT psoriatic mice. Compared with WT mice,TET2-/- dermatitis lesions were more severe and progressed faster,and the psoriasis area and severity index (PASI) score and spleen index were higher. The mRNA expression levels of TNF-α,IL-6,IL-17A and IL-23 in the skin lesions of TET2-/- mice were higher than those of WT mice. The epidermal thickening and inflammatory cell infiltration were more significant in TET2-/- mice. The expression of IL-17,INF-γ and TNF-α in the skin lesions of TET2-/- mice was significantly higher than that of WT mice. Ultrastructural pathological observation showed that the cell junction disappeared in the skin lesions of TET2-/- mice,and there was a mass of mitochondrial ridges broken and dissolved,mitochondrial vacuoles,and the texture of the mitochondrial membrane became darker. Conclusion Loss of TET2 promotes the inflammatory response and exacerbates IMQ induced psoriasis-like dermatitis injury in mice.