title: Technical advance: Langerhans cells derived from a human cell line in a full-thickness skin equivalent undergo allergen-induced maturation and migration.
abstract: In this report, the construction of a functional, immunocompetent, full-thickness skin equivalent (SE) is described, consisting of an epidermal compartment containing keratinocytes, melanocytes, and human LCs derived from the MUTZ-3 cell line (MUTZ-LC) and a fibroblast-populated dermal compartment. The CD1a(+)Langerin(+)HLA-DR(+) MUTZ-LCs populate the entire epidermis at a similar density to that found in native skin. Exposure of the SE to subtoxic concentrations of the allergens NiSO(4) and resorcinol resulted in LC migration out of the epidermis toward the fibroblast-populated dermal compartment. A significant dose-dependent up-regulation of the DC maturation-related CCR7 and IL-1β transcripts and of CD83 at the protein level upon epidermal exposure to both allergens was observed, indicative of maturation and migration of the epidermally incorporated LC. We have thus successfully developed a reproducible and functional full-thickness SE model containing epidermal MUTZ-LC. This model offers an alternative to animal testing for identifying potential chemical sensitizers and for skin-based vaccination strategies and provides a unique research tool to study human LC biology in situ under controlled in vitro conditions.
authors.affiliation: Department of Dermatology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Krista
authors.initials: K
authors.lastname: Ouwehand
authors.forename: Sander W
authors.initials: SW
authors.lastname: Spiekstra
authors.forename: Taco
authors.initials: T
authors.lastname: Waaijman
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: Tanja D
authors.initials: TD
authors.lastname: de Gruijl
authors.forename: Susan
authors.initials: S
authors.lastname: Gibbs
mesh_terms: D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology; D007801:Langerhans Cells / Q000166:cytology* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D009924:Organ Culture Techniques; D054400:Receptors, CCR7 / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D023822:Tissue Engineering; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D007136:Immunoglobulins; D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D054400:Receptors, CCR7; D000097802:CD83 Antigen; C515370:CCR7 protein, human