title: Activation of Langerhans cells promotes the inflammation in imiquimod-induced psoriasis-like dermatitis.
abstract: 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.
  
  
  OBJECTIVE
  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 (γδ T cells and neutrophils) and inflammatory cytokine expression (IL-17, IL-22, IL-23 and tumor necrosis factor-α). After application with IMQ, LCs expanded in epidermis and showed increased expression of CD80 and CD86, and migrated to draining lymph node within 48h. LCs in the lymph node 48h after application with IMQ expressed increased level of CD80, CD86, CD40 and CC chemokine receptor 7.
  
  
  CONCLUSIONS
  LCs were activated upon application with IMQ, and promoted the inflammatory responses in psoriasis-like dermatitis.
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Chunying
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Zhenlai
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Jixin
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Fu
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu 210042, China; Jiangsu Provincial Key Laboratory of Molecular Biology for Skin Diseases and STIs, China. Electronic address: dryao_xu@126.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, China. Electronic address: liweiderma@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D000634:Aminoquinolines / Q000633:toxicity; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000954:Antigens, Surface / Q000235:genetics; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D000078404:Epidermal Cells; D004817:Epidermis / Q000473:pathology; D005434:Flow Cytometry; D000077271:Imiquimod; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics; D008198:Lymph Nodes / Q000166:cytology; D037241:Mannose-Binding Lectins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011565:Psoriasis / Q000139:chemically induced / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha
chemical_list: D000634:Aminoquinolines; D015703:Antigens, CD; D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D016207:Cytokines; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D014409:Tumor Necrosis Factor-alpha; D000077271:Imiquimod
keywords: Activation; Imiquimod; Inflammation; Langerhans cells; Psoriasis