title: IL-23 from Langerhans cells is required for the development of imiquimod-induced psoriasis-like dermatitis by induction of IL-17A-producing γδ T cells.
abstract: Psoriasis is a common chronic inflammatory skin disease that involves dysregulated interplay between immune cells and keratinocytes. Recently, it has been reported that IL-23 induces CCR6+ γδ T cells, which have the pivotal role in psoriasis-like skin inflammation in mice of producing IL-17A and IL-22. Langerhans cells (LCs) are a subset of dendritic cells that reside in the epidermis and regulate immune responses. The role of LCs has been extensively investigated in contact hypersensitivity, but their role in psoriasis remains to be clarified. In this study, we focused on Th17-related factors and assessed the role of LCs and γδ T cells in the development of psoriasis using a mouse psoriasis model triggered by topical application of imiquimod (IMQ). LC depletion by means of diphtheria toxin (DT) in Langerin DT receptor-knocked-in mice suppressed hyperkeratosis, parakeratosis, and ear swelling in the IMQ-treated regions. In addition, LC-depleted mice showed decreased levels of Th17-related cytokines in IMQ-treated skin lesions. Moreover, the IMQ-treated skin of LC-depleted mice showed a decreased number of IL-17A-producing CCR6+ γδ T cells. These results suggest that LCs are required for the development of psoriasis-like lesions induced by IMQ in mice.
authors.affiliation: Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan. Electronic address: yockey@med.uoeh-u.ac.jp.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Yoshiki
authors.affiliation: Department of Dermatology, Kyoto University, Kyoto, Japan. Electronic address: kaba@kuhp.kyoto-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
authors.affiliation: Department of Dermatology, Kyoto University, Kyoto, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Honda
authors.affiliation: Department of Dermatology, Kyoto University, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakamizo
authors.affiliation: Department of Dermatology, Kyoto University, Kyoto, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sawada
authors.affiliation: Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Sugita
authors.affiliation: Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Yoshioka
authors.affiliation: Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Ohmori
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale U631, Centre National de la Recherche Scientifique UMR6102, Université de la Méditerrannée, Marseille, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.affiliation: Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Tokura
authors.affiliation: Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Motonobu
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D003877:Dermatitis, Contact / Q000276:immunology; D004195:Disease Models, Animal; D000077271:Imiquimod; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D053760:Interleukin-23 Subunit p19 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D011565:Psoriasis / Q000139:chemically induced / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D054399:Receptors, CCR6 / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000077271:Imiquimod; D018664:Interleukin-12; D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054399:Receptors, CCR6; D000097043:Interleukin-22; C498126:CCR6 protein, mouse; C098680:Il17a protein, mouse; C508841:Il23a protein, mouse