Minseok Lee1, Sung Hee Kim1, Tae-Gyun Kim1, Jeyun Park2, Jae Won Lee1, Min-Geol Lee3. 1. Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, South Korea. 2. Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, South Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. 3. Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, South Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: mglee@yuhs.ac.
Abstract
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.
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.
Authors: Tamara Moreno-Sosa; María Belén Sánchez; Elisa Olivia Pietrobon; Juan Manuel Fernandez-Muñoz; Felipe Carlos Martín Zoppino; Flavia Judith Neira; María José Germanó; Diego Esteban Cargnelutti; Alicia Carolina Innocenti; Graciela Alma Jahn; Susana Ruth Valdez; Juan Pablo Mackern-Oberti Journal: Front Immunol Date: 2021-04-29 Impact factor: 7.561