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 Il23a and accordingly demonstrated an attenuated cytokine production of IL-17A and IL-22 from γδlow 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.
Bibliographical noteFunding Information:
This study was supported by a faculty research grant of Yonsei University College of Medicine ( 6-2011-0149 ), by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health and Welfare (HI17C1659 to MGL), by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2015R1D1A1A01060527 to MGL; NRF-2017R1D1A1B03035571 to TGK), and by the NRF grant funded by the Korea government (Ministry of Science and ICT) (NRF-2018R1A2B6007818 to MGL).
All Science Journal Classification (ASJC) codes
- Molecular Biology