title: E-cadherin interactions are required for Langerhans cell differentiation.
abstract: Human skin contains the following two distinct DC subsets: (i) Langerhans cells (LCs), expressing Langerin but not DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), are predominantly localized in the epidermis; and (ii) dermal DCs, expressing DC-SIGN but not Langerin, are observed mainly in the dermis. It is not known whether localization in the epidermis provides cues for LC differentiation. Here, we show that E-cadherin expressed by epidermal keratinocytes (KCs) is crucial for differentiation of LCs. Monocytes differentiated into LC-like cells in presence of IL-4, GM-CSF, and TGF-β1. However, these LC-like cells expressed not only Langerin but also DC-SIGN. Notably, co-culturing of these LC-like cells with KCs expressing E-cadherin or recombinant E-cadherin strongly decreased expression of DC-SIGN and further induced a phenotype similar to purified epidermal LCs. Moreover, pretreatment of LC-like cells with anti-E-cadherin-specific antibody completely abolished their Langerin expression, indicating the requirement of E-cadherin-E-cadherin interactions for the differentiation into Langerin(+)  cells. These findings suggest that E-cadherin expressed by KCs provide environmental cues that induce differentiation of LCs in the epidermis.
authors.affiliation: Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Mayumi
authors.forename: Eri
authors.initials: E
authors.lastname: Watanabe
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Norose
authors.forename: Eiji
authors.initials: E
authors.lastname: Watari
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawana
authors.forename: Teunis B H
authors.initials: TB
authors.lastname: Geijtenbeek
authors.forename: Hidemi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D020405:Dermis / Q000276:immunology*; D004817:Epidermis / Q000276:immunology*; D006801:Humans; D015603:Keratinocytes / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D019138:Antibodies, Blocking; D015703:Antigens, CD; D015820:Cadherins; D015815:Cell Adhesion Molecules; D016207:Cytokines; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C121916:CD207 protein, human