Resident and monocyte-derived Langerhans cells are required for imiquimod-induced psoriasis-like dermatitis model

Background: Langerhans cells (LCs) are dendritic cells that reside in the epidermis and local inflammation results in an increased differentiation of monocyte-derived LCs. Only few studies have investigated on the role of LCs in psoriasis-like dermatitis model, but the results are variable and the exact role of LCs in psoriasis model remains to be elucidated. Objective: To explore the functional role of resident (rLCs) and monocyte-derived LCs (mLCs) in imiquimod (IMQ)-induced psoriasis-like inflammation using human Langerin-diphtheria toxin subunit A (huLang-DTA) mice. Methods: 5% IMQ cream was topically applied on the skins. Clinical and histopathological features were evaluated. Psoriasis-related gene expression was analyzed by quantitative polymerase chain reaction. The production of psoriasis-related cytokines including IL-17A and IL-22 by T cells were assessed by flow cytometry from the lesional skins. Results: huLang-DTA mice showed a common depletion of both rLCs and mLCs in the IMQ-treated skins. huLang-DTA mice had a reduced IMQ-induced psoriasis-like inflammation featuring erythema, scale, and thickness compared with wild-type mice. Psoriatic lesions from huLang-DTA mice had a decreased level of 1123a and accordingly demonstrated an attenuated cytokine production of IL-17A and IL-22 from gamma delta(low) T cells. mLCs revealed a significantly greater level of IL-23 expression compared to rLCs in response to topical IMQ treatment. Conclusion: Although both rLCs and mLCs are involved in the development of IMQ-induced psoriasis-like dermatitis, inflammation -induced mLCs present a superior capacity for producing IL-23 in this murine experimental model of psoriasis. (C) 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.