Background: In psoriasis, the inflammatory cell infiltrate consists mainly of dendritic cells (DCs), macrophages and T cells in the dermis and neutrophils in the epidermis. Langerhans cells (LCs) is a member of DCs that reside in the epidermis. The functional role of LCs has been studied but exact role of LCs in psoraisis is still controversial. There are few studies to explore the role of LCs in psoriasis-like model but results was variable Objectives: Explore the functional role of LCs in imiquimod (IMQ)-induced psoriasis-like model using human langerin-diphtheria toxin (huLangerin-DTA) mice Methods: IMQ cream was topically applied on the ear and back skin of mice for 6 consecutive days. Clinical and histopathological features were evaluated. Frequencies of psoriasis related cells and production of cytokines including IL-17A and IL-22 were measured by flow cytometry. mRNA expression level was analyzed using qRT-PCR from the local skin. Results: huLangerin-DTA mice showed a partially reduced clinical inflammatory score of IMQ-induced psoriasis-like inflammation compared with wild type mice. huLangerin-DTA mice demonstrated a significantly decreased infiltration of EpCAMhiCD103. resident and/or monocyte-derived LCs in the IMQ-induced lesions. IL22-producing γδTCR+ T cells were reduced which was correlated with a lesser local IL-22 mRNA expression Conclusion: LCs and related induction of IL-22 are required for the maximal development of psoriasis-like lesions induced by IMQ in mice.