title: Distinct behavior of human Langerhans cells and inflammatory dendritic epidermal cells at tight junctions in patients with atopic dermatitis.
abstract: BACKGROUND
  The stratum corneum and tight junctions (TJs) form physical barriers in the epidermis. Dendrites of activated Langerhans cells (LCs) extend beyond the TJs to capture external antigens in mice. LCs and inflammatory dendritic epidermal cells (IDECs) are observed in the skin of patients with atopic dermatitis (AD).
  
  
  OBJECTIVE
  We sought to investigate the characteristics of LCs and IDECs and the distribution of their antigen capture receptors in relation to TJs in normal and AD skin.
  
  
  METHODS
  We characterized the interactions of LCs and IDECs with TJs and the expression patterns of langerin and FcεRI by using whole-mount epidermal sheets from healthy subjects and patients with AD, ichthyosis vulgaris, and psoriasis vulgaris.
  
  
  RESULTS
  As in mouse skin, activated LCs penetrate TJs in human skin. The number of LCs with TJ penetration increased approximately 5-fold in erythematous lesional skin of patients with AD but not in nonlesional skin of patients with AD or lesions of patients with ichthyosis vulgaris or psoriasis. In contrast, IDECs localized in the lower part of the epidermis, and their dendrites extended horizontally without penetration through TJs. Although langerin accumulated on the tips of dendrites of activated LCs, FcεRI was expressed diffusely on the cell surfaces on LCs and IDECs in lesional skin from patients with AD.
  
  
  CONCLUSIONS
  These findings highlight interesting differences between LCs and IDECs in epidermis of patients with AD, where LCs, but not IDECs, extend dendrites through the TJs, likely to capture antigens from outside the TJ barrier with a polarized distribution of langerin but not FcεRI. These behavioral differences between skin dendritic cells might reflect an important pathophysiology of AD.
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan; Department of Dermatology, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan; Keio-Maruho Laboratory of Skin Barriology, Keio University School of Medicine, Tokyo, Japan. Electronic address: akiharu@a5.keio.jp.
authors.forename: Akiharu
authors.initials: A
authors.lastname: Kubo
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan; KOSÉ Endowed Program for Skin Care and Allergy Prevention, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Harumi
authors.initials: H
authors.lastname: Fujita
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Yokouchi
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan; Department of Dermatology, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawasaki
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Nomura
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: Center for Clinical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kouyama
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Ebihara
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nagao
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan; Keio-Maruho Laboratory of Skin Barriology, Keio University School of Medicine, Tokyo, Japan; KOSÉ Endowed Program for Skin Care and Allergy Prevention, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Amagai
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000150:complications / Q000276:immunology*; D004817:Epidermis / Q000473:pathology; D006801:Humans; D016112:Ichthyosis Vulgaris / Q000150:complications / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009924:Organ Culture Techniques; D011565:Psoriasis / Q000150:complications / Q000276:immunology*; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D059467:Transcriptome
chemical_list: D015703:Antigens, CD; C121916:CD207 protein, human; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D017455:Receptors, IgE
keywords: FcεRI; Langerhans cell; atopic dermatitis; inflammatory dendritic epidermal cell; langerin; stratum corneum; tight junction