Activation of Langerhans cells promotes the inflammation in imiquimod-induced psoriasis-like dermatitis

Background: Langerhans cells (LCs) are epidermis-resident dendritic cells that sense and mediate stimuli from skin and outside world, and participate in various skin diseases, playing either pro-inflammatory or regulatory roles. However, the exact function of LCs in the pathogenesis of psoriasis remains unclear, and the conclusions of previous studies are controversial. Objectives: To explore the role of LCs in mouse model of imiquimod (IMQ)-induced psoriasis-like dermatitis using langerin-diphtheria toxin A (DTA) mice that are constitutively deficient in LCs. Methods: IMQ (Aldara) was painted on the skin of mice to produce psoriasis-like dermatitis, and inflammation was evaluated by gross ear thickness, histopathology, flow cytometry and cytokine production. Bone marrow transplantation and fluorescein isothiocyanate tracing were applied to access the migration of LCs. Results: The severity of IMQ-induced dermatitis in langerin-DTA mice was significantly lower than that of wild-type mice, as evidenced by decreased level of ear thickness, inflammatory cell infiltration (gamma delta T cells and neutrophils) and inflammatory cytokine expression (IL-17, IL-22, IL-23 and tumor necrosis factor-alpha). After application with IMQ LCs expanded in epidermis and showed increased expression of CD80 and CD86, and migrated to draining lymph node within 48 h. LCs in the lymph node 48 h after application with IMQ expressed increased level of CD80, CD86, CD40 and CC chemokine receptor 7. Conclusion: LCs were activated upon application with IMQ and promoted the inflammatory responses in psoriasis-like dermatitis. (C) 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.